Interactional role of microRNAs and bHLH-PAS proteins in cancer (Review)

Li,Yumin; Wei,Yucai; Guo,Jiwu; Cheng,Yusheng; He,Wenting

doi:10.3892/ijo.2015.3007

Interactional role of microRNAs and bHLH-PAS proteins in cancer (Review)

Authors:
- Yumin Li
- Yucai Wei
- Jiwu Guo
- Yusheng Cheng
- Wenting He
View Affiliations

Affiliations: The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
Published online on: May 15, 2015 https://doi.org/10.3892/ijo.2015.3007
Pages: 25-34

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs) are recognized as an emerging class of master regulators that regulate human gene expression at the post-transcriptional level and are involved in many normal and pathological cellular processes. Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcriptional regulators that sense and respond to environmental signals (such as chemical pollutants) or to physiological signals (for instance hypoxia). In the normal state, bHLH-PAS proteins are responsible for multiple critical aspects of physiology to ensure the cell accurate homeostasis, but dysregulation of these proteins has been shown to contribute to carcinogenic events such as tumor initiation, promotion, and progression. Increasing epidemiological and experimental studies have shown that bHLH-PAS proteins regulate a panel of miRNAs, whereas some miRNAs also target bHLH-PAS proteins. The interaction between miRNAs and certain bHLH-PAS proteins [hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR)] is relevant to many vital events associated with tumorigenesis. This review will summarize recent findings on the interesting and complicated underlying mechanisms that miRNAs interact with HIFs or AHR in tumors, hopefully to benefit the discovery of novel drug-interfering targets for cancer therapy.

View Figures

View References

1	Lai EC: Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 30:363–364. 2002. View Article : Google Scholar : PubMed/NCBI
2	Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R and Rajewsky N: Widespread changes in protein synthesis induced by microRNAs. Nature. 455:58–63. 2008. View Article : Google Scholar : PubMed/NCBI
3	Isomoto H, Matsushima K, Inoue N, Hayashi T, Nakayama T, Kunizaki M, Hidaka S, Nakayama M, Hisatsune J, Nakashima M, et al: Interweaving microRNAs and proinflammatory cytokines in gastric mucosa with reference to H. pylori infection. J Clin Immunol. 32:290–299. 2012. View Article : Google Scholar
4	Schoof CR, Botelho EL, Izzotti A and Vasques Ldos R: MicroRNAs in cancer treatment and prognosis. Am J Cancer Res. 2:414–433. 2012.PubMed/NCBI
5	Mendell JT and Olson EN: MicroRNAs in stress signaling and human disease. Cell. 148:1172–1187. 2012. View Article : Google Scholar : PubMed/NCBI
6	Tili E, Michaille JJ and Croce CM: MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer. Immunol Rev. 253:167–184. 2013. View Article : Google Scholar : PubMed/NCBI
7	Denison MS, Soshilov AA, He G, DeGroot DE and Zhao B: Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. Toxicol Sci. 124:1–22. 2011. View Article : Google Scholar : PubMed/NCBI
8	McIntosh BE, Hogenesch JB and Bradfield CA: Mammalian Per-Arnt-Sim proteins in environmental adaptation. Annu Rev Physiol. 72:625–645. 2010. View Article : Google Scholar : PubMed/NCBI
9	Feng S, Cao Z and Wang X: Role of aryl hydrocarbon receptor in cancer. Biochim Biophys Acta. 1836:197–210. 2013.PubMed/NCBI
10	Shen G, Li X, Jia YF, Piazza GA and Xi Y: Hypoxia-regulated microRNAs in human cancer. Acta Pharmacol Sin. 34:336–341. 2013. View Article : Google Scholar : PubMed/NCBI
11	Hay MP, Hicks KO and Wang J: Hypoxia-directed drug strategies to target the tumor microenvironment. Adv Exp Med Biol. 772:111–145. 2014. View Article : Google Scholar
12	Safe S, Lee SO and Jin UH: Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target. Toxicol Sci. 135:1–16. 2013. View Article : Google Scholar : PubMed/NCBI
13	Agrawal R, Pandey P, Jha P, Dwivedi V, Sarkar C and Kulshreshtha R: Hypoxic signature of microRNAs in glioblastoma: Insights from small RNA deep sequencing. BMC Genomics. 15:6862014. View Article : Google Scholar : PubMed/NCBI
14	Grosso S, Doyen J, Parks SK, Bertero T, Paye A, Cardinaud B, Gounon P, Lacas-Gervais S, Noël A, Pouysségur J, et al: MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. Cell Death Dis. 4:e5442013. View Article : Google Scholar : PubMed/NCBI
15	Nakada C, Tsukamoto Y, Matsuura K, Nguyen TL, Hijiya N, Uchida T, Sato F, Mimata H, Seto M and Moriyama M: Overexpression of miR-210, a downstream target of HIF1α, causes centrosome amplification in renal carcinoma cells. J Pathol. 224:280–288. 2011. View Article : Google Scholar : PubMed/NCBI
16	Chen Z, Li Y, Zhang H, Huang P and Luthra R: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene. 29:4362–4368. 2010. View Article : Google Scholar : PubMed/NCBI
17	Camps C, Saini HK, Mole DR, Choudhry H, Reczko M, Guerra-Assunção JA, Tian YM, Buffa FM, Harris AL, Hatzigeorgiou AG, et al: Integrated analysis of microRNA and mRNA expression and association with HIF binding reveals the complexity of microRNA expression regulation under hypoxia. Mol Cancer. 13:282014. View Article : Google Scholar : PubMed/NCBI
18	Bruning U, Cerone L, Neufeld Z, Fitzpatrick SF, Cheong A, Scholz CC, Simpson DA, Leonard MO, Tambuwala MM, Cummins EP, et al: MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol Cell Biol. 31:4087–4096. 2011. View Article : Google Scholar : PubMed/NCBI
19	He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Jiang BH and Liu LZ: Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/ COX-2 pathway. Environ Health Perspect. 122:255–261. 2014.PubMed/NCBI
20	Lei Z, Li B, Yang Z, Fang H, Zhang GM, Feng ZH and Huang B: Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration. PLoS One. 4:e76292009. View Article : Google Scholar : PubMed/NCBI
21	Rane S, He M, Sayed D, Vashistha H, Malhotra A, Sadoshima J, Vatner DE, Vatner SF and Abdellatif M: Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ Res. 104:879–886. 2009. View Article : Google Scholar : PubMed/NCBI
22	Gits CM, van Kuijk PF, de Rijck JC, Muskens N, Jonkers MB, van IJcken WF, Mathijssen RH, Verweij J, Sleijfer S and Wiemer EA: MicroRNA response to hypoxic stress in soft tissue sarcoma cells: microRNA mediated regulation of HIF3α. BMC Cancer. 14:4292014. View Article : Google Scholar
23	Ghosh G, Subramanian IV, Adhikari N, Zhang X, Joshi HP, Basi D, Chandrashekhar YS, Hall JL, Roy S, Zeng Y, et al: Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis. J Clin Invest. 120:4141–4154. 2010. View Article : Google Scholar : PubMed/NCBI
24	Gordon MW, Yan F, Zhong X, Mazumder PB, Xu-Monette ZY, Zou D, Young KH, Ramos KS and Li Y: Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma. Mol Carcinog. May 6–2014.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
25	Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT and Giaccia AJ: Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell. 35:856–867. 2009. View Article : Google Scholar : PubMed/NCBI
26	Wang H, Bian S and Yang CS: Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating miR-210 expression caused by stabilizing HIF-1α. Carcinogenesis. 32:1881–1889. 2011. View Article : Google Scholar : PubMed/NCBI
27	Li L, Huang K, You Y, Fu X, Hu L, Song L and Meng Y: Hypoxia-induced miR-210 in epithelial ovarian cancer enhances cancer cell viability via promoting proliferation and inhibiting apoptosis. Int J Oncol. 44:2111–2120. 2014.PubMed/NCBI
28	Hwang HW, Baxter LL, Loftus SK, Cronin JC, Trivedi NS, Borate B and Pavan WJ: Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A. Pigment Cell Melanoma Res. 27:777–787. 2014. View Article : Google Scholar : PubMed/NCBI
29	Mace TA, Collins AL, Wojcik SE, Croce CM, Lesinski GB and Bloomston M: Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells. J Surg Res. 184:855–860. 2013. View Article : Google Scholar : PubMed/NCBI
30	Ding G, Huang G, Liu HD, Liang HX, Ni YF, Ding ZH, Ni GY and Hua HW: MiR-199a suppresses the hypoxia-induced proliferation of non-small cell lung cancer cells through targeting HIF1α. Mol Cell Biochem. 384:173–180. 2013. View Article : Google Scholar : PubMed/NCBI
31	Jia XQ, Cheng HQ, Qian X, Bian CX, Shi ZM, Zhang JP, Jiang BH and Feng ZQ: Lentivirus-mediated overexpression of microRNA-199a inhibits cell proliferation of human hepatocellular carcinoma. Cell Biochem Biophys. 62:237–244. 2012. View Article : Google Scholar
32	Shang W, Chen X, Nie L, Xu M, Chen N, Zeng H and Zhou Q: miR199b suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in prostate cancer cells. Int J Mol Sci. 14:8422–8436. 2013. View Article : Google Scholar : PubMed/NCBI
33	Zhang L, Sun ZJ, Bian Y and Kulkarni AB: MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma. Cancer Lett. 331:230–238. 2013. View Article : Google Scholar : PubMed/NCBI
34	Taguchi A, Yanagisawa K, Tanaka M, Cao K, Matsuyama Y, Goto H and Takahashi T: Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17–92 microRNA cluster. Cancer Res. 68:5540–5545. 2008. View Article : Google Scholar : PubMed/NCBI
35	Trivellin G, Butz H, Delhove J, Igreja S, Chahal HS, Zivkovic V, McKay T, Patócs A, Grossman AB and Korbonits M: MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro. Am J Physiol Endocrinol Metab. 303:E708–E719. 2012. View Article : Google Scholar : PubMed/NCBI
36	Duan H, Jiang Y, Zhang H and Wu Y: MiR-320 and miR-494 affect cell cycles of primary murine bronchial epithelial cells exposed to benzo[a]pyrene. Toxicol In Vitro. 24:928–935. 2010. View Article : Google Scholar
37	Yuan Q, Loya K, Rani B, Möbus S, Balakrishnan A, Lamle J, Cathomen T, Vogel A, Manns MP, Ott M, et al: MicroRNA-221 overexpression accelerates hepatocyte proliferation during liver regeneration. Hepatology. 57:299–310. 2013. View Article : Google Scholar
38	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
39	Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD and Semenza GL: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 16:4604–4613. 1996.PubMed/NCBI
40	Roman AC, Carvajal-Gonzalez JM, Rico-Leo EM and Fernandez-Salguero PM: Dioxin receptor deficiency impairs angiogenesis by a mechanism involving VEGF-A depletion in the endothelium and transforming growth factor-beta overexpression in the stroma. J Biol Chem. 284:25135–25148. 2009. View Article : Google Scholar : PubMed/NCBI
41	Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP and Gurtner GC: Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 10:858–864. 2004. View Article : Google Scholar : PubMed/NCBI
42	Wu YY, Chen YL, Jao YC, Hsieh IS, Chang KC and Hong TM: miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1. Angiogenesis. 17:247–260. 2014. View Article : Google Scholar
43	Ramakrishnan S, Anand V and Roy S: Vascular endothelial growth factor signaling in hypoxia and inflammation. J Neuroimmune Pharmacol. 9:142–160. 2014. View Article : Google Scholar : PubMed/NCBI
44	Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, Kung HF, Lai L and Jiang BH: MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS One. 6:e191392011. View Article : Google Scholar
45	Cascio S, D’Andrea A, Ferla R, Surmacz E, Gulotta E, Amodeo V, Bazan V, Gebbia N and Russo A: miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol. 224:242–249. 2010.PubMed/NCBI
46	He J, Jing Y, Li W, Qian X, Xu Q, Li FS, Liu LZ, Jiang BH and Jiang Y: Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis. PLoS One. 8:e566472013. View Article : Google Scholar : PubMed/NCBI
47	Yamakuchi M, Yagi S, Ito T and Lowenstein CJ: MicroRNA-22 regulates hypoxia signaling in colon cancer cells. PLoS One. 6:e202912011. View Article : Google Scholar : PubMed/NCBI
48	Zhou B, Ma R, Si W, Li S, Xu Y, Tu X and Wang Q: MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growth. Cancer Lett. 333:159–169. 2013. View Article : Google Scholar : PubMed/NCBI
49	Shi ZM, Wang J, Yan Z, You YP, Li CY, Qian X, Yin Y, Zhao P, Wang YY, Wang XF, et al: MiR-128 inhibits tumor growth and angiogenesis by targeting p70S6K1. PLoS One. 7:e327092012. View Article : Google Scholar : PubMed/NCBI
50	Xu Q, Liu LZ, Qian X, Chen Q, Jiang Y, Li D, Lai L and Jiang BH: MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis. Nucleic Acids Res. 40:761–774. 2012. View Article : Google Scholar :
51	Cha ST, Chen PS, Johansson G, Chu CY, Wang MY, Jeng YM, Yu SL, Chen JS, Chang KJ, Jee SH, et al: MicroRNA-519c suppresses hypoxia-inducible factor-1alpha expression and tumor angiogenesis. Cancer Res. 70:2675–2685. 2010. View Article : Google Scholar : PubMed/NCBI
52	Xue G, Yan HL, Zhang Y, Hao LQ, Zhu XT, Mei Q and Sun SH: c-Myc-mediated repression of miR-15–16 in hypoxia is induced by increased HIF-2alpha and promotes tumor angiogenesis and metastasis by upregulating FGF2. Oncogene. 34:1393–1406. 2015. View Article : Google Scholar
53	Zhang S, Kim K, Jin UH, Pfent C, Cao H, Amendt B, Liu X, Wilson-Robles H and Safe S: Aryl hydrocarbon receptor agonists induce microRNA-335 expression and inhibit lung metastasis of estrogen receptor negative breast cancer cells. Mol Cancer Ther. 11:108–118. 2012. View Article : Google Scholar :
54	Yeh YM, Chuang CM, Chao KC and Wang LH: MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1alpha. Int J Cancer. 133:867–878. 2013. View Article : Google Scholar : PubMed/NCBI
55	Joshi HP, Subramanian IV, Schnettler EK, Ghosh G, Rupaimoole R, Evans C, Saluja M, Jing Y, Cristina I, Roy S, et al: Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis. Proc Natl Acad Sci USA. 111:5331–5336. 2014. View Article : Google Scholar : PubMed/NCBI
56	Zhang H, Pu J, Qi T, Qi M, Yang C, Li S, Huang K, Zheng L and Tong Q: MicroRNA-145 inhibits the growth, invasion, metastasis and angiogenesis of neuroblastoma cells through targeting hypoxia-inducible factor 2 alpha. Oncogene. 33:387–397. 2014. View Article : Google Scholar
57	Chen L, Han L, Zhang K, Shi Z, Zhang J, Zhang A, Wang Y, Song Y, Li Y, Jiang T, et al: VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1α/VEGF and β-catenin/Tcf-4 signaling. Neuro-oncol. 14:1026–1036. 2012. View Article : Google Scholar
58	Cao P, Deng Z, Wan M, Huang W, Cramer SD, Xu J, Lei M and Sui G: MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1alpha/ HIF-1beta. Mol Cancer. 9:1082010. View Article : Google Scholar
59	Chio CC, Lin JW, Cheng HA, Chiu WT, Wang YH, Wang JJ, Hsing CH and Chen RM: MicroRNA-210 targets antiapoptotic Bcl-2 expression and mediates hypoxia-induced apoptosis of neuroblastoma cells. Arch Toxicol. 87:459–468. 2013. View Article : Google Scholar
60	Yang W, Sun T, Cao J, Liu F, Tian Y and Zhu W: Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro. Exp Cell Res. 318:944–954. 2012. View Article : Google Scholar : PubMed/NCBI
61	Hecht E, Zago M, Sarill M, Rico de Souza A, Gomez A, Matthews J, Hamid Q, Eidelman DH and Baglole CJ: Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation. Toxicol Appl Pharmacol. 280:511–525. 2014. View Article : Google Scholar : PubMed/NCBI
62	Aisenberg AC and Potter VR: Studies on the Pasteur effect. II Specific mechanisms. J Biol Chem. 224:1115–1127. 1957.PubMed/NCBI
63	Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL and Loscalzo J: MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab. 10:273–284. 2009. View Article : Google Scholar : PubMed/NCBI
64	McCormick RI, Blick C, Ragoussis J, Schoedel J, Mole DR, Young AC, Selby PJ, Banks RE and Harris AL: miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis. Br J Cancer. 108:1133–1142. 2013. View Article : Google Scholar : PubMed/NCBI
65	Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, et al: MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS One. 5:e103452010. View Article : Google Scholar : PubMed/NCBI
66	He M, Lu Y, Xu S, Mao L, Zhang L, Duan W, Liu C, Pi H, Zhang Y, Zhong M, et al: MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron-sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells. Cell Death Dis. 5:e10902014. View Article : Google Scholar : PubMed/NCBI
67	Puisségur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand K, Cardinaud B, Hofman V, et al: miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ. 18:465–478. 2011. View Article : Google Scholar :
68	Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, et al: An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem. 284:35134–35143. 2009. View Article : Google Scholar : PubMed/NCBI
69	Tanaka H, Sasayama T, Tanaka K, Nakamizo S, Nishihara M, Mizukawa K, Kohta M, Koyama J, Miyake S, Taniguchi M, et al: MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells. J Neurooncol. 111:273–283. 2013. View Article : Google Scholar
70	Li W, Wang J, Chen QD, Qian X, Li Q, Yin Y, Shi ZM, Wang L, Lin J, Liu LZ, et al: Insulin promotes glucose consumption via regulation of miR-99a/mTOR/PKM2 pathway. PLoS One. 8:e649242013. View Article : Google Scholar : PubMed/NCBI
71	Li D, Liu C, Yu H, et al: AhR is negatively regulated by miR-203 in response to TCDD or BaP treatment. Toxicol Res (Camb). 2:142–151. 2013.
72	Nguyen NT, Nakahama T, Le DH, Van Son L, Chu HH and Kishimoto T: Aryl hydrocarbon receptor and kynurenine: Recent advances in autoimmune disease research. Front Immunol. 5:5512014. View Article : Google Scholar : PubMed/NCBI
73	Wang H, Flach H, Onizawa M, Wei L, McManus MT and Weiss A: Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210. Nat Immunol. 15:393–401. 2014. View Article : Google Scholar : PubMed/NCBI
74	Xu Z, Zhao L, Zhu LY, He M, Zheng L and Wu Y: MicroRNA-17, 20a regulates the proangiogenic function of tumor-associated macrophages via targeting hypoxia-inducible factor 2α. PLoS One. 8:e778902013. View Article : Google Scholar
75	Poitz DM, Augstein A, Gradehand C, Ende G, Schmeisser A and Strasser RH: Regulation of the Hif-system by micro-RNA 17 and 20a - role during monocyte-to-macrophage differentiation. Mol Immunol. 56:442–451. 2013. View Article : Google Scholar : PubMed/NCBI
76	Csak T, Bala S, Lippai D, Satishchandran A, Catalano D, Kodys K and Szabo G: microRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis. Liver Int. 35:532–541. 2015. View Article : Google Scholar
77	Bleck B, Grunig G, Chiu A, Liu M, Gordon T, Kazeros A and Reibman J: MicroRNA-375 regulation of thymic stromal lymphopoietin by diesel exhaust particles and ambient particulate matter in human bronchial epithelial cells. J Immunol. 190:3757–3763. 2013. View Article : Google Scholar : PubMed/NCBI
78	Nakahama T, Hanieh H, Nguyen NT, Chinen I, Ripley B, Millrine D, Lee S, Nyati KK, Dubey PK, Chowdhury K, et al: Aryl hydrocarbon receptor-mediated induction of the microRNA-132/212 cluster promotes interleukin-17-producing T-helper cell differentiation. Proc Natl Acad Sci USA. 110:11964–11969. 2013. View Article : Google Scholar : PubMed/NCBI
79	Yang W, Wei J, Guo T, Shen Y and Liu F: Knockdown of miR-210 decreases hypoxic glioma stem cells stemness and radioresistance. Exp Cell Res. 326:22–35. 2014. View Article : Google Scholar : PubMed/NCBI
80	Papi A, Storci G, Guarnieri T, De Carolis S, Bertoni S, Avenia N, Sanguinetti A, Sidoni A, Santini D, Ceccarelli C, et al: Peroxisome proliferator activated receptor-α/hypoxia inducible factor-1α interplay sustains carbonic anhydrase IX and apoliprotein E expression in breast cancer stem cells. PLoS One. 8:e549682013. View Article : Google Scholar
81	Han M, Wang Y, Liu M, Bi X, Bao J, Zeng N, Zhu Z, Mo Z, Wu C and Chen X: MiR-21 regulates epithelial-mesenchymal transition phenotype and hypoxia-inducible factor-1α expression in third-sphere forming breast cancer stem cell-like cells. Cancer Sci. 103:1058–1064. 2012. View Article : Google Scholar : PubMed/NCBI
82	Zhang KL, Zhou X, Han L, Chen LY, Chen LC, Shi ZD, Yang M, Ren Y, Yang JX, Frank TS, et al: MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimo-tuzumab. Mol Cancer. 13:632014. View Article : Google Scholar
83	Bao B, Ali S, Ahmad A, Azmi AS, Li Y, Banerjee S, Kong D, Sethi S, Aboukameel A, Padhye SB, et al: Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment. PLoS One. 7:e501652012. View Article : Google Scholar : PubMed/NCBI
84	Bao B, Ahmad A, Kong D, Ali S, Azmi AS, Li Y, Banerjee S, Padhye S and Sarkar FH: Hypoxia induced aggressiveness of prostate cancer cells is linked with deregulated expression of VEGF, IL-6 and miRNAs that are attenuated by CDF. PLoS One. 7:e437262012. View Article : Google Scholar : PubMed/NCBI
85	Babar IA, Czochor J, Steinmetz A, Weidhaas JB, Glazer PM and Slack FJ: Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells. Cancer Biol Ther. 12:908–914. 2011. View Article : Google Scholar : PubMed/NCBI
86	Kang SG, Lee WH, Lee YH, Lee YS and Kim SG: Hypoxia-inducible factor-1α inhibition by a pyrrolopyrazine metabolite of oltipraz as a consequence of microRNAs 199a-5p and 20a induction. Carcinogenesis. 33:661–669. 2012. View Article : Google Scholar : PubMed/NCBI
87	Wang C, Song B, Song W, Liu J, Sun A, Wu D, Yu H, Lian J, Chen L and Han J: Underexpressed microRNA-199b-5p targets hypoxia-inducible factor-1α in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients. J Gastroenterol Hepatol. 26:1630–1637. 2011. View Article : Google Scholar : PubMed/NCBI
88	Hu W, Zhao J and Pei G: Activation of aryl hydrocarbon receptor (ahr) by tranilast, an anti-allergy drug, promotes miR-302 expression and cell reprogramming. J Biol Chem. 288:22972–22984. 2013. View Article : Google Scholar : PubMed/NCBI
89	Joo MS, Lee CG, Koo JH and Kim SG: miR-125b transcriptionally increased by Nrf2 inhibits AhR repressor, which protects kidney from cisplatin-induced injury. Cell Death Dis. 4:e8992013. View Article : Google Scholar : PubMed/NCBI
90	Dejean E, Renalier MH, Foisseau M, Agirre X, Joseph N, de Paiva GR, Al Saati T, Soulier J, Desjobert C, Lamant L, et al: Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas. Leukemia. 25:1882–1890. 2011. View Article : Google Scholar : PubMed/NCBI
91	He M, Wang QY, Yin QQ, Tang J, Lu Y, Zhou CX, Duan CW, Hong DL, Tanaka T, Chen GQ, et al: HIF-1α downregulates miR-17/20a directly targeting p21 and STAT3: A role in myeloid leukemic cell differentiation. Cell Death Differ. 20:408–418. 2013. View Article : Google Scholar :
92	Bertozzi D, Marinello J, Manzo SG, Fornari F, Gramantieri L and Capranico G: The natural inhibitor of DNA topoisomerase I, camptothecin, modulates HIF-1α activity by changing miR expression patterns in human cancer cells. Mol Cancer Ther. 13:239–248. 2014. View Article : Google Scholar
93	Lichner Z, Mejia-Guerrero S, Ignacak M, Krizova A, Bao TT, Girgis AH, Youssef YM and Yousef GM: Pleiotropic action of renal cell carcinoma-dysregulated miRNAs on hypoxia-related signaling pathways. Am J Pathol. 180:1675–1687. 2012. View Article : Google Scholar : PubMed/NCBI
94	Kao SY, Tsai MM, Wu CH, Chen JJ, Tseng SH, Lin SC and Chan KW: Co-targeting of multiple microRNAs on factor-inhibiting hypoxia-inducible factor (FIH) gene for the pathogenesis of head and neck carcinomas. Head Neck. Oct 28–2014.(Epub ahead of print). View Article : Google Scholar
95	Mathew LK, Lee SS, Skuli N, Rao S, Keith B, Nathanson KL, Lal P and Simon MC: Restricted expression of miR-30c-2-3p and miR-30a-3p in clear cell renal cell carcinomas enhances HIF2α activity. Cancer Discov. 4:53–60. 2014. View Article : Google Scholar :
96	Liu CJ, Tsai MM, Hung PS, Kao SY, Liu TY, Wu KJ, Chiou SH, Lin SC and Chang KW: miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma. Cancer Res. 70:1635–1644. 2010. View Article : Google Scholar : PubMed/NCBI
97	Ghosh AK, Shanafelt TD, Cimmino A, Taccioli C, Volinia S, Liu CG, Calin GA, Croce CM, Chan DA, Giaccia AJ, et al: Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood. 113:5568–5574. 2009. View Article : Google Scholar : PubMed/NCBI
98	Yang Z, Han Y, Cheng K, Zhang G and Wang X: miR-99a directly targets the mTOR signalling pathway in breast cancer side population cells. Cell Prolif. 47:587–595. 2014. View Article : Google Scholar : PubMed/NCBI
99	Blick C, Ramachandran A, Wigfield S, McCormick R, Jubb A, Buffa FM, Turley H, Knowles MA, Cranston D, Catto J, et al: Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer. Br J Cancer. 109:50–59. 2013. View Article : Google Scholar : PubMed/NCBI
100	Tao T, Li G, Dong Q, Liu D, Liu C, Han D, Huang Y, Chen S, Xu B and Chen M: Loss of SNAIL inhibits cellular growth and metabolism through the miR-128-mediated RPS6KB1/ HIF-1alpha/PKM2 signaling pathway in prostate cancer cells. Tumour Biol. 35:8543–8550. 2014. View Article : Google Scholar : PubMed/NCBI
101	Umezu T, Tadokoro H, Azuma K, Yoshizawa S, Ohyashiki K and Ohyashiki JH: Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1. Blood. 124:3748–3757. 2014. View Article : Google Scholar : PubMed/NCBI
102	Song T, Zhang X, Wang C, Wu Y, Cai W, Gao J and Hong B: MiR-138 suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in clear cell renal cell carcinoma 786-O cells. Asian Pac J Cancer Prev. 12:1307–1311. 2011.
103	Yin Y, Yan ZP, Lu NN, Xu Q, He J, Qian X, Yu J, Guan X, Jiang BH and Liu LZ: Downregulation of miR-145 associated with cancer progression and VEGF transcriptional activation by targeting N-RAS and IRS1. Biochim Biophys Acta. 1829:239–247. 2013. View Article : Google Scholar
104	Yu ZY, Bai YN, Luo LX, Wu H and Zeng Y: Expression of microRNA-150 targeting vascular endothelial growth factor-A is downregulated under hypoxia during liver regeneration. Mol Med Rep. 8:287–293. 2013.PubMed/NCBI
105	Sun X, Wei L, Chen Q and Terek RM: MicroRNA regulates vascular endothelial growth factor expression in chondrosarcoma cells. Clin Orthop Relat Res. 473:907–913. 2014. View Article : Google Scholar : PubMed/NCBI
106	Song Z, Ren H, Gao S, Zhao T, Wang X, Zhang S, Zhao X, Jia L, Sun J and Hao J: The hypoxia-inducible factor-1 regulates the microRNA185 expression through binding to hypoxia response elements sequence 2. Med Oncol. 30:7562013. View Article : Google Scholar : PubMed/NCBI
107	Raimondi L, Amodio N, Di Martino MT, Altomare E, Leotta M, Caracciolo D, Gullà A, Neri A, Taverna S, D’Aquila P, et al: Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: In vitro and in vivo anti-tumor activity. Oncotarget. 5:3039–3054. 2014.PubMed/NCBI
108	Qu A, Du L, Yang Y, Liu H, Li J, Wang L, Liu Y, Dong Z, Zhang X, Jiang X, et al: Hypoxia-inducible MiR-210 is an independent prognostic factor and contributes to metastasis in colorectal cancer. PLoS One. 9:e909522014. View Article : Google Scholar : PubMed/NCBI
109	Crosby ME, Kulshreshtha R, Ivan M and Glazer PM: MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 69:1221–1229. 2009. View Article : Google Scholar : PubMed/NCBI
110	Kim HW, Haider HK, Jiang S and Ashraf M: Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem. 284:33161–33168. 2009. View Article : Google Scholar : PubMed/NCBI
111	Mathew LK, Skuli N, Mucaj V, Lee SS, Zinn PO, Sathyan P, Imtiyaz HZ, Zhang Z, Davuluri RV, Rao S, et al: miR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma. Proc Natl Acad Sci USA. 111:291–296. 2014. View Article : Google Scholar :
112	Xu H, Zhao L, Fang Q, Sun J, Zhang S, Zhan C, Liu S and Zhang Y: MiR-338–3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α. PLoS One. 9:e1155652014. View Article : Google Scholar
113	Sohn EJ, Won G, Lee J, Lee S and Kim SH: Upregulation of miRNA3195 and miRNA374b mediates the anti-angiogenic properties of melatonin in hypoxic PC-3 prostate cancer cells. J Cancer. 6:19–28. 2015. View Article : Google Scholar : PubMed/NCBI
114	Seok JK, Lee SH, Kim MJ and Lee YM: MicroRNA-382 induced by HIF-1α is an angiogenic miR targeting the tumor suppressor phosphatase and tensin homolog. Nucleic Acids Res. 42:8062–8072. 2014. View Article : Google Scholar : PubMed/NCBI
115	Zhang D, Shi Z, Li M and Mi J: Hypoxia-induced miR-424 decreases tumor sensitivity to chemotherapy by inhibiting apoptosis. Cell Death Dis. 5:e13012014. View Article : Google Scholar : PubMed/NCBI
116	Oda Y, Nakajima M, Mohri T, Takamiya M, Aoki Y, Fukami T and Yokoi T: Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24. Toxicol Appl Pharmacol. 260:222–231. 2012. View Article : Google Scholar : PubMed/NCBI
117	Huang TC, Chang HY, Chen CY, Wu PY, Lee H, Liao YF, Hsu WM, Huang HC and Juan HF: Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR. FEBS Lett. 585:3582–3586. 2011. View Article : Google Scholar : PubMed/NCBI