microRNA‑144 inhibits cell proliferation and invasion by directly targeting TIGAR in esophageal carcinoma

Mu,Yushu; Wang,Qifei; Tan,Lei; Lin,Lin; Zhang,Benhua

doi:10.3892/ol.2020.11420

microRNA‑144 inhibits cell proliferation and invasion by directly targeting TIGAR in esophageal carcinoma

Authors:
- Yushu Mu
- Qifei Wang
- Lei Tan
- Lin Lin
- Benhua Zhang
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Affiliations: Department of Thoracic Surgery, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China, Department of Thoracic Surgery, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China, Department of Digestive Medicine, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China, Department of Oncology, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China
Published online on: February 24, 2020 https://doi.org/10.3892/ol.2020.11420
Pages: 3079-3088
Copyright: © Mu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

microRNAs (miRNAs) have been identified to play vital roles in the development and progression of numerous different types of human malignancy, including esophageal squamous cell carcinoma (ESCC). In the present study, the biological function of microRNA‑144 (miR‑144) was investigated, as well as its underlying molecular mechanism in ESCC. The results revealed that miR‑144 expression was significantly decreased, whereas the expression of TP53‑inducible glycolysis and apoptosis regulator (TIGAR) was significantly increased in human ESCC tissues when compared with adjacent non‑tumor tissues. An increase in TIGAR was significantly associated with tumor size and Tumor‑Node‑Metastasis staging in patients. Functional analysis revealed that the overexpression of miR‑144 using lentivirus particles significantly inhibited cell proliferation and tumor colony formation, and induced cell apoptosis in EC9706 and EC109 cells. The autophagy activity was also enhanced by miR‑144 activity. In addition, overexpression of miR‑144 significantly inhibited tumor growth in vivo. In the present study, TIGAR was confirmed to be the downstream target of miR‑144 in ESCC. siRNA‑mediated downregulation of TIGAR inversely regulated the inhibition effect of miR‑144 on ESCC cells. To conclude, the present study demonstrated that miR‑144 inhibits proliferation and invasion in esophageal cancer by directly targeting TIGAR.

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1	Bai Y, Lin H, Fang Z, Luo Q, Fang Y, Su Y, Hu Q, Duan H, Chen F and Zhang ZY: Plasma microRNA-19a as a potential biomarker for esophageal squamous cell carcinoma diagnosis and prognosis. Biomark Med. 11:431–441. 2017. View Article : Google Scholar : PubMed/NCBI
2	Cao Z, Zheng X, Cao L and Liang N: MicroRNA-539 inhibits the epithelial-mesenchymal transition of esophageal cancer cells by twist-related protein 1-mediated modulation of melanoma associated antigen A4. Oncol Res. 26:529–536. 2018. View Article : Google Scholar : PubMed/NCBI
3	Cui XB, Peng H, Li RR, Mu JQ, Yang L, Li N, Liu CX, Hu JM, Li SG, Wei Y, et al: MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic PLCE1 in Kazakh esophageal squamous cell carcinoma. Oncotarget. 8:92454–92469. 2017. View Article : Google Scholar : PubMed/NCBI
4	Fong LY, Taccioli C, Jing R, Smalley KJ, Alder H, Jiang Y, Fadda P, Farber JL and Croce CM: MicroRNA dysregulation and esophageal cancer development depend on the extent of zinc dietary deficiency. Oncotarget. 7:10723–10738. 2016. View Article : Google Scholar : PubMed/NCBI
5	Chen M, Xia Y, Tan Y, Jiang G, Jin H and Chen Y: Downregulation of microRNA-370 in esophageal squamous-cell carcinoma is associated with cancer progression and promotes cancer cell proliferation via upregulating PIN1. Gene. 661:68–77. 2018. View Article : Google Scholar : PubMed/NCBI
6	Chen Z, Zhao L, Zhao F, Yang G and Wang J: MicroRNA-26b regulates cancer proliferation migration and cell cycle transition by suppressing TRAF5 in esophageal squamous cell carcinoma. Am J Transl Res. 8:1957–1970. 2016.PubMed/NCBI
7	Dong W, Li B, Wang J, Song Y, Zhang Z, Fu C and Zhang P: Diagnostic and predictive significance of serum microRNA-7 in esophageal squamous cell carcinoma. Oncol Rep. 35:1449–1456. 2016. View Article : Google Scholar : PubMed/NCBI
8	Gao X, Wang X, Cai K, Wang W, Ju Q, Yang X, Wang H and Wu H: MicroRNA-127 is a tumor suppressor in human esophageal squamous cell carcinoma through the regulation of oncogene FMNL3. Eur J Pharmacol. 791:603–610. 2016. View Article : Google Scholar : PubMed/NCBI
9	He W, Feng J, Zhang Y, Wang Y, Zang W and Zhao G: microRNA-186 inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma by targeting SKP2. Lab Invest. 96:317–324. 2016. View Article : Google Scholar : PubMed/NCBI
10	Ji HH, Hong L, Huang GL, Yin HX, Xu P, Luo SY and Song JK: Association between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 polymorphisms and esophageal cancer risk: A meta-analysis. Meta Gene. 3:14–25. 2015. View Article : Google Scholar : PubMed/NCBI
11	Wu N, Song Y, Pang L and Chen Z: CRCT1 regulated by microRNA-520 g inhibits proliferation and induces apoptosis in esophageal squamous cell cancer. Tumour Biol. 37:8271–8279. 2016. View Article : Google Scholar : PubMed/NCBI
12	Yu Q, Liu Y, Wen C, Zhao Y, Jin S, Hu Y, Wang F, Chen L, Zhang B, Wang W, et al: MicroRNA-1 inhibits tumorigenicity of esophageal squamous cell carcinoma and enhances sensitivity to gefitinib. Oncol Lett. 15:963–971. 2018.PubMed/NCBI
13	Bulibu J, Wang W, Tang Y, Li N and Saifuding K: Association between polymorphisms in the promoter region of microRNA-34b/c and the chemoradiotherapy efficacy for locally advanced esophageal squamous cell carcinoma in Chinese Han population. Pathol Oncol Res. 25:421–427. 2019. View Article : Google Scholar : PubMed/NCBI
14	Harada K, Baba Y, Ishimoto T, Kosumi K, Tokunaga R, Izumi D, Ohuchi M, Nakamura K, Kiyozumi Y, Kurashige J, et al: Suppressor microRNA-145 is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma. Anticancer Res. 35:4617–4624. 2015.PubMed/NCBI
15	Chan CM, Lai KK, Ng EK, Kiang MN, Kwok TW, Wang HK, Chan KW, Law TT, Tong DK, Chan KT, et al: Serum microRNA-193b as a promising biomarker for prediction of chemoradiation sensitivity in esophageal squamous cell carcinoma patients. Oncol Lett. 15:3273–3280. 2018.PubMed/NCBI
16	Dong S, Yin H, Dong C, Sun K, Lv P, Meng W, Ming L and He F: Predictive value of plasma MicroRNA-216a/b in the diagnosis of esophageal squamous cell carcinoma. Dis Markers. 2016:18570672016. View Article : Google Scholar : PubMed/NCBI
17	Fan YX, Bian XH, Qian PD, Chen ZZ, Wen J, Luo YH, Yan PW and Zhang Q: MicroRNA-125b inhibits cell proliferation and induces cell apoptosis in esophageal squamous cell carcinoma by targeting BMF. Oncol Rep. 40:61–72. 2018.PubMed/NCBI
18	Berry MF: Esophageal cancer: Staging system and guidelines for staging and treatment. J Thorac Dis. 6 (Suppl 3):S289–S297. 2014.PubMed/NCBI
19	Liu L, Wang S, Chen R, Wu Y, Zhang B, Huang S, Zhang J, Xiao F, Wang M and Liang Y: Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562. Biochem Biophys Res Commun. 425:368–373. 2012. View Article : Google Scholar : PubMed/NCBI
20	Whitman SP, Maharry K, Radmacher MD, Becker H, Mrózek K, Margeson D, Holland KB, Wu YZ, Schwind S, Metzeler KH, et al: FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: A Cancer and Leukemia Group B study. Blood. 116:3622–3626. 2010. View Article : Google Scholar : PubMed/NCBI
21	Gao Z, Liu R, Liao J, Yang M, Pan E, Yin L and Pu Y: Possible tumor suppressive role of the miR-144/451 cluster in esophageal carcinoma as determined by principal component regression analysis. Mol Med Rep. 14:3805–3813. 2016. View Article : Google Scholar : PubMed/NCBI
22	Wu W, Hou W, Wu Z, Wang Y, Yi Y and Lin W: miRNA-144 in the saliva is a genetic marker for early diagnosis of esophageal cancer. Nan Fang Yi Ke Da Xue Xue Bao. 33:1783–1786. 2013.(In Chinese). PubMed/NCBI
23	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
24	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:2015. View Article : Google Scholar
25	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
26	Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, Dalamagas T and Hatzigeorgiou AG: DIANA-miRPath v3.0: Deciphering microRNA function with experimental support. Nucleic Acids Res. 43:W460–W466. 2015. View Article : Google Scholar : PubMed/NCBI
27	Hu C, Lv L, Peng J, Liu D, Wang X, Zhou Y and Huo J: MicroRNA-375 suppresses esophageal cancer cell growth and invasion by repressing metadherin expression. Oncol Lett. 13:4769–4775. 2017. View Article : Google Scholar : PubMed/NCBI
28	Zhang ZQ, Cao Z, Liu C, Li R, Wang WD and Wang XY: MiRNA-embedded ShRNAs for radiation-inducible LGMN knockdown and the antitumor effects on breast cancer. PLoS One. 11:e01634462016. View Article : Google Scholar : PubMed/NCBI
29	Dong S, Yin H, Dong C, Sun K, Lv P, Meng W, Ming L and He F: Corrigendum to ‘Predictive value of plasma MicroRNA-216a/b in the diagnosis of esophageal squamous cell carcinoma’. Dis Markers. 2017:34376792017. View Article : Google Scholar : PubMed/NCBI
30	Fong LY, Farber JL and Croce CM: Zinc intake, microRNA dysregulation, and esophageal cancer. Aging (Albany NY). 8:1161–1162. 2016. View Article : Google Scholar : PubMed/NCBI
31	Cui H, Zhang S, Zhou H and Guo L: Direct downregulation of B-cell translocation gene 3 by microRNA-93 is required for desensitizing esophageal cancer to radiotherapy. Dig Dis Sci. 62:1995–2003. 2017. View Article : Google Scholar : PubMed/NCBI
32	Fan JY, Yang Y, Xie JY, Lu YL, Shi K and Huang YQ: MicroRNA-144 mediates metabolic shift in ovarian cancer cells by directly targeting Glut1. Tumour Biol. 37:6855–6860. 2016. View Article : Google Scholar : PubMed/NCBI
33	Huang J, Shi Y, Li H, Yang M and Liu G: MicroRNA-144 acts as a tumor suppressor by targeting Rho-associated coiled-coil containing protein kinase 1 in osteosarcoma cells. Mol Med Rep. 12:4554–4559. 2015. View Article : Google Scholar : PubMed/NCBI
34	Huo F, Zhang C, He H and Wang Y: MicroRNA-144-3p inhibits proliferation and induces apoptosis of human salivary adenoid carcinoma cells via targeting of mTOR. Biotechnol Lett. 38:409–416. 2016. View Article : Google Scholar : PubMed/NCBI
35	Jin J, Wang Y, Xu Y, Zhou X, Liu Y, Li X and Wang J: MicroRNA-144 regulates cancer cell proliferation and cell-cycle transition in acute lymphoblastic leukemia through the interaction of FMN2. J Gene Med. 19:2017. View Article : Google Scholar
36	Li B, Zhang S, Shen H and Li C: MicroRNA-144-3p suppresses gastric cancer progression by inhibiting epithelial-to-mesenchymal transition through targeting PBX3. Biochem Biophys Res Commun. 484:241–247. 2017. View Article : Google Scholar : PubMed/NCBI
37	Li D, Li H, Yang Y and Kang L: Long noncoding RNA urothelial carcinoma associated 1 promotes the proliferation and metastasis of human lung tumor cells by regulating MicroRNA-144. Oncol Res. 26:537–546. 2018. View Article : Google Scholar : PubMed/NCBI
38	Lin L, Zheng Y, Tu Y, Wang Z, Liu H, Lu X, Xu L and Yuan J: MicroRNA-144 suppresses tumorigenesis and tumor progression of astrocytoma by targeting EZH2. Hum Pathol. 46:971–980. 2015. View Article : Google Scholar : PubMed/NCBI
39	Cheng AM, Byrom MW, Shelton J and Ford LP: Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 33:1290–1297. 2005. View Article : Google Scholar : PubMed/NCBI
40	Zhang LY, Ho-Fun Lee V, Wong AM, Kwong DL, Zhu YH, Dong SS, Kong KL, Chen J, Tsao SW, Guan XY and Fu L: MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN. Carcinogenesis. 34:454–463. 2013. View Article : Google Scholar : PubMed/NCBI
41	Shao Y, Li P, Zhu ST, Yue JP, Ji XJ, Ma D, Wang L, Wang YJ, Zong Y, Wu YD and Zhang ST: MiR-26a and miR-144 inhibit proliferation and metastasis of esophageal squamous cell cancer by inhibiting cyclooxygenase-2. Oncotarget. 7:15173–15186. 2016. View Article : Google Scholar : PubMed/NCBI
42	Ko YH, Domingo-Vidal M, Roche M, Lin Z, Whitaker-Menezes D, Seifert E, Capparelli C, Tuluc M, Birbe RC, Tassone P, et al: TP53-inducible glycolysis and apoptosis regulator (TIGAR) metabolically reprograms carcinoma and stromal cells in breast cancer. J Biol Chem. 291:26291–26303. 2016. View Article : Google Scholar : PubMed/NCBI
43	Xu X, Liu C and Bao J: Hypoxia-induced hsa-miR-101 promotes glycolysis by targeting TIGAR mRNA in clear cell renal cell carcinoma. Mol Med Rep. 15:1373–1378. 2017. View Article : Google Scholar : PubMed/NCBI