MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF‑1R-mediated AKT and ERK pathways Retraction in /10.3892/or.2022.8339

Zhou,Fangzheng; Nie,Long; Feng,Dali; Guo,Siyan; Luo,Ren'na

doi:10.3892/or.2017.5835

MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF‑1R-mediated AKT and ERK pathways

Retraction in: /10.3892/or.2022.8339

Authors:
- Fangzheng Zhou
- Long Nie
- Dali Feng
- Siyan Guo
- Ren'na Luo
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Affiliations: Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei 441399, P.R. China, Department of Radiotherapy and Chemotherapy, The Second People's Hospital of Yichang, Yichang, Hubei 43000, P.R. China
Published online on: July 18, 2017 https://doi.org/10.3892/or.2017.5835
Pages: 1857-1866

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Abstract

Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR‑379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR‑379 was downregulated in both NSCLC tissue and cell lines. Low miR‑379 expression in NSCLC tissues was significantly correlated with TNM stage and lymph node metastasis. In addition, functional experiments revealed that restoring the expression of miR‑379 inhibited cell proliferation, migration and invasion of NSCLC. The insulin-like growth factor receptor-1 (IGF‑1R) was identified as a direct target of miR‑379 in NSCLC. IGF‑1R was highly expressed in NSCLC tissues and inversely correlated with miR‑379 expression. Downregulation of IGF‑1R had tumor suppressive roles similar to that of miR‑379 overexpression on NSCLC cell proliferation, migration and invasion. Moreover, the upregulation of IGF‑1R effectively rescued the tumor suppressive roles induced by miR‑379 overexpression in NSCLC. The resumption of the expression of miR‑379 inhibited the activation of AKT and ERK signaling pathways in NSCLC. These findings suggested that miR‑379 acts as a tumor suppressor in NSCLC by directly targeting IGF‑1R and indirectly regulating AKT and ERK signaling pathways. miR‑379 provides novel therapeutic targets for the treatment of patients with this disease.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Zeng H, Zhang S and He J: Annual report on status of cancer in China, 2011. Chin J Cancer Res. 27:2–12. 2015. View Article : Google Scholar : PubMed/NCBI
3	Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA, Diekemper R, Detterbeck FC and Arenberg DA: Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 143:(Suppl. 5). eS314–S340. 2013. View Article : Google Scholar
4	Cao Q, Mao ZD, Shi YJ, Chen Y, Sun Y, Zhang Q, Song L and Peng LP: MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway. Oncotarget. 7:77468–77481. 2016.PubMed/NCBI
5	Xu W, Yang G, Xu Y, Zhang Q, Fu Q, Yu J, Yu M, Zhao W, Yang Z, Hu F, et al: The possibility of traditional Chinese Medicine as maintenance therapy for advanced nonsmall cell lung cancer. Evid Based Complement Alternat Med. 2014:2789172014. View Article : Google Scholar : PubMed/NCBI
6	Zarogoulidis K, Zarogoulidis P, Darwiche K, Boutsikou E, Machairiotis N, Tsakiridis K, Katsikogiannis N, Kougioumtzi I, Karapantzos I, Huang H, et al: Treatment of non-small cell lung cancer (NSCLC). J Thorac Dis. 5:(Suppl 4). S389–S396. 2013.PubMed/NCBI
7	Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, Kunkler I, et al: EUROCARE-4 Working Group: Recent cancer survival in Europe: A 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol. 8:784–796. 2007. View Article : Google Scholar : PubMed/NCBI
8	Highlights in NSCLC from the 2014 American Society of Clinical Oncology annual meeting. Clin Adv Hematol Oncol. 12:(Suppl 18). S7–S16. 2014.
9	Mountain CF: Revisions in the International System for Staging Lung Cancer. Chest. 111:1710–1717. 1997. View Article : Google Scholar : PubMed/NCBI
10	Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG and Shepherd FA: Non-small-cell lung cancer. Lancet. 378:1727–1740. 2011. View Article : Google Scholar : PubMed/NCBI
11	Rosell R, Bivona TG and Karachaliou N: Genetics and biomarkers in personalisation of lung cancer treatment. Lancet. 382:720–731. 2013. View Article : Google Scholar : PubMed/NCBI
12	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
13	Jiang L, Liu X, Chen Z, Jin Y, Heidbreder CE, Kolokythas A, Wang A, Dai Y and Zhou X: MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Biochem J. 432:199–205. 2010. View Article : Google Scholar : PubMed/NCBI
14	Xiong Y, Zhang L, Holloway AK, Wu X, Su L and Kebebew E: MiR-886-3p regulates cell proliferation and migration, and is dysregulated in familial non-medullary thyroid cancer. PLoS One. 6:e247172011. View Article : Google Scholar : PubMed/NCBI
15	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
16	Kloosterman WP and Plasterk RH: The diverse functions of microRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI
17	Broderick JA and Zamore PD: MicroRNA therapeutics. Gene Ther. 18:1104–1110. 2011. View Article : Google Scholar : PubMed/NCBI
18	Li C, Dong J, Han Z and Zhang K: MicroRNA-219-5p represses the proliferation, migration, and invasion of gastric cancer cells by targeting the LRH-1/Wnt/b-catenin signaling pathway. Oncol Res. 25:617–627. 2017. View Article : Google Scholar : PubMed/NCBI
19	Wu SG, Huang YJ, Bao B, Wu LM, Dong J, Liu XH, Li ZH, Wang XY, Wang L, Chen BJ, et al: miR-508-5p acts as an anti-oncogene by targeting MESDC1 in hepatocellular carcinoma. Neoplasma. 64:40–47. 2017. View Article : Google Scholar : PubMed/NCBI
20	Li JZ, Li J, Wang HQ, Li X, Wen B and Wang YJ: MiR-141-3p promotes prostate cancer cell proliferation through inhibiting kruppel-like factor-9 expression. Biochem Biophys Res Commun. 482:1381–1386. 2017. View Article : Google Scholar : PubMed/NCBI
21	Wu D, Niu X, Pan H, Zhou Y, Zhang Z, Qu P and Zhou J: Tumor-suppressing effects of microRNA-429 in human renal cell carcinoma via the downregulation of Sp1. Oncol Lett. 12:2906–2911. 2016.PubMed/NCBI
22	Ma J, Yu J, Liu J, Yang X, Lou M, Liu J, Feng F, Ji P and Wang L: MicroRNA-302a targets GAB2 to suppress cell proliferation, migration and invasion of glioma. Oncol Rep. 37:1159–1167. 2017.PubMed/NCBI
23	Ma W, Ma CN, Zhou NN, Li XD and Zhang YJ: Up-regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy. Sci Rep. 6:316512016. View Article : Google Scholar : PubMed/NCBI
24	Maugeri-Saccà M, Coppola V, Bonci D and De Maria R: MicroRNAs and prostate cancer: From preclinical research to translational oncology. Cancer J. 18:253–261. 2012. View Article : Google Scholar : PubMed/NCBI
25	Khan S, Brougham CL, Ryan J, Sahrudin A, O'Neill G, Wall D, Curran C, Newell J, Kerin MJ and Dwyer RM: miR-379 regulates cyclin B1 expression and is decreased in breast cancer. PLoS One. 8:e687532013. View Article : Google Scholar : PubMed/NCBI
26	Gururajan M, Josson S, Chu GC, Lu CL, Lu YT, Haga CL, Zhau HE, Liu C, Lichterman J, Duan P, et al: miR-154* and miR-379 in the DLK1-DIO3 microRNA mega-cluster regulate epithelial to mesenchymal transition and bone metastasis of prostate cancer. Clin Cancer Res. 20:6559–6569. 2014. View Article : Google Scholar : PubMed/NCBI
27	Chen JS, Li HS, Huang JQ, Dong SH, Huang ZJ, Yi W, Zhan GF, Feng JT, Sun JC and Huang XH: MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma. Cancer Lett. 375:73–83. 2016. View Article : Google Scholar : PubMed/NCBI
28	Li Z, Shen J, Chan MT and Wu WK: MicroRNA-379 suppresses osteosarcoma progression by targeting PDK1. J Cell Mol Med. 21:315–323. 2017. View Article : Google Scholar : PubMed/NCBI
29	Hao GJ, Hao HJ, Ding YH, Wen H, Li XF, Wang QR and Zhang BB: Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells. FEBS Lett. 591:636–645. 2017. View Article : Google Scholar : PubMed/NCBI
30	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
31	Yin M, Guan X, Liao Z and Wei Q: Insulin-like growth factor-1 receptor-targeted therapy for non-small cell lung cancer: A mini review. Am J Transl Res. 1:101–114. 2009.PubMed/NCBI
32	Qian J, Dong A, Kong M, Ma Z, Fan J and Jiang G: Suppression of type 1 insulin-like growth factor receptor expression by small interfering RNA inhibits A549 human lung cancer cell invasion in vitro and metastasis in xenograft nude mice. Acta Biochim Biophys Sin (Shanghai). 39:137–147. 2007. View Article : Google Scholar : PubMed/NCBI
33	Kim YH, Sumiyoshi S, Hashimoto S, Masago K, Togashi Y, Sakamori Y, Okuda C, Mio T and Mishima M: Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer. Clin Lung Cancer. 13:385–390. 2012. View Article : Google Scholar : PubMed/NCBI
34	Cao H, Dong W, Shen H, Xu J, Zhu L, Liu Q and Du J: Combinational therapy enhances the effects of anti-IGF-1R mAb Figitumumab to target small cell lung cancer. PLoS One. 10:e01358442015. View Article : Google Scholar : PubMed/NCBI
35	Zhang W, Liu K, Liu S, Ji B, Wang Y and Liu Y: MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma. Tumour Biol. 36:9779–9788. 2015. View Article : Google Scholar : PubMed/NCBI
36	Osaki LH and Gama P: MAPKs and signal transduction in the control of gastrointestinal epithelial cell proliferation and differentiation. Int J Mol Sci. 14:10143–10161. 2013. View Article : Google Scholar : PubMed/NCBI
37	Cao Z, Liu LZ, Dixon DA, Zheng JZ, Chandran B and Jiang BH: Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells. Cell Signal. 19:1542–1553. 2007. View Article : Google Scholar : PubMed/NCBI
38	Li Z, Li B, Niu L and Ge L: miR-592 functions as a tumor suppressor in human non-small cell lung cancer by targeting SOX9. Oncol Rep. 37:297–304. 2017.PubMed/NCBI
39	Li H, Ouyang R, Wang Z, Zhou W, Chen H, Jiang Y, Zhang Y, Li H, Liao M, Wang W, et al: MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4. Sci Rep. 6:390012016. View Article : Google Scholar : PubMed/NCBI
40	Pei K, Zhu JJ, Wang CE, Xie QL and Guo JY: MicroRNA-185-5p modulates chemosensitivity of human non-small cell lung cancer to cisplatin via targeting ABCC1. Eur Rev Med Pharmacol Sci. 20:4697–4704. 2016.PubMed/NCBI
41	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
42	Yamamoto K, Seike M, Takeuchi S, Soeno C, Miyanaga A, Noro R, Minegishi Y, Kubota K and Gemma A: MiR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma. Oncol Rep. 32:2365–2372. 2014.PubMed/NCBI
43	Hu Q, Gong JP, Li J, Zhong SL, Chen WX, Zhang JY, Ma TF, Ji H, Lv MM, Zhao JH, et al: Down-regulation of miRNA-452 is associated with adriamycin-resistance in breast cancer cells. Asian Pac J Cancer Prev. 15:5137–5142. 2014. View Article : Google Scholar : PubMed/NCBI
44	Li ECJ, Shao D, Zhang D, Pan Y, Chen L and Zhang X: The insulin-like growth factor-I receptor inhibitor picropodophyllin-induced selective apoptosis of hepatocellular carcinoma cell through a caspase-dependent mitochondrial pathway. Oncol Res. 21:103–110. 2013.PubMed/NCBI
45	Wang YH, Han XD, Qiu Y, Xiong J, Yu Y, Wang B, Zhu ZZ, Qian BP, Chen YX, Wang SF, et al: Increased expression of insulin-like growth factor-1 receptor is correlated with tumor metastasis and prognosis in patients with osteosarcoma. J Surg Oncol. 105:235–243. 2012. View Article : Google Scholar : PubMed/NCBI
46	Ma Y, Cheng Q, Ren Z, Xu L, Zhao Y, Sun J, Hu S and Xiao W: Induction of IGF-1R expression by EGR-1 facilitates the growth of prostate cancer cells. Cancer Lett. 317:150–156. 2012. View Article : Google Scholar : PubMed/NCBI
47	Sichani MM, Yazdi FS, Moghaddam NA, Chehrei A, Kabiri M, Naeimi A and Taheri D: Prognostic value of insulin- like growth factor-I receptor expression in renal cell carcinoma. Saudi J Kidney Dis Transpl. 21:69–74. 2010.PubMed/NCBI
48	Gryko M, Kiśluk J, Cepowicz D, Zińczuk J, Kamocki Z, Guzińska-Ustymowicz K, Pryczynicz A, Czyżewska J, Kemona A and Kędra B: Expression of insulin-like growth factor receptor type 1 correlate with lymphatic metastases in human gastric cancer. Pol J Pathol. 65:135–140. 2014. View Article : Google Scholar : PubMed/NCBI
49	Xie QX, Lin XC, Zhang MF, Han CX and Guo YH: Expression of IGF-I and IGF-IR in bladder cancer. Chin J Cancer. 23:707–709. 2004.(In Chinese).
50	Pollak MN: Insulin-like growth factors and neoplasia. Novartis Found Symp. 262:84–98; discussion 98–107, 265–268. 2004. View Article : Google Scholar : PubMed/NCBI
51	Werner H and LeRoith D: The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 68:183–223. 1996. View Article : Google Scholar : PubMed/NCBI
52	Pollak M: The insulin and insulin-like growth factor receptor family in neoplasia: An update. Nat Rev Cancer. 12:159–169. 2012.PubMed/NCBI
53	King H, Aleksic T, Haluska P and Macaulay VM: Can we unlock the potential of IGF-1R inhibition in cancer therapy? Cancer Treat Rev. 40:1096–1105. 2014. View Article : Google Scholar : PubMed/NCBI
54	Tsuta K, Mimae T, Nitta H, Yoshida A, Maeshima AM, Asamura H, Grogan TM, Furuta K and Tsuda H: Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas. Hum Pathol. 44:975–982. 2013. View Article : Google Scholar : PubMed/NCBI
55	Zhang X, Sun J, Wang H, Lou Y, Zhang Y, Sha H, Feng J and Han B: IGF-1R and Bmi-1 expressions in lung adenocarcinoma and their clinicopathologic and prognostic significance. Tumour Biol. 35:739–745. 2014. View Article : Google Scholar : PubMed/NCBI
56	Wei YH, Tang HX, Liao YD, Fu SL, Xu LQ, Chen G, Zhang C, Ju S, Liu ZG, You LK, et al: Effects of insulin-like growth factor 1 receptor and its inhibitor AG1024 on the progress of lung cancer. J Huazhong Univ Sci Technolog Med Sci. 35:834–841. 2015. View Article : Google Scholar : PubMed/NCBI