miR-92a-3p promotes the proliferation, migration and invasion of esophageal squamous cell cancer by regulating PTEN

Li,Xin; Guo,Shuilong; Min,Li; Guo,Qingdong; Zhang,Shutian

doi:10.3892/ijmm.2019.4258

miR-92a-3p promotes the proliferation, migration and invasion of esophageal squamous cell cancer by regulating PTEN

Authors:
- Xin Li
- Shuilong Guo
- Li Min
- Qingdong Guo
- Shutian Zhang
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Affiliations: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China,
Published online on: June 27, 2019 https://doi.org/10.3892/ijmm.2019.4258
Pages: 973-981
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Esophageal squamous cell cancer (ESCC) has a high mortality rate. MicroRNA (miR)‑92a‑3p is considered to be a tumor promotor and an oncomiR. The aim of the present study was to investigate the effect of miR‑92a‑3p and its target gene on ESCC in terms of proliferation, migration and invasion. Higher expression of miR‑92a‑3p was detected in the tissues of patients with ESCC, compared with that in normal tissues. In addition, ESCC cell lines had a higher expression of miR‑92a‑3p compared with normal esophageal cells. A miR‑92a‑3p mimic was found to promote ESCC cell proliferation and a miR‑92a‑3p inhibitor was found to reduce ESCC cell proliferation. miR‑92a‑3p mimic transfection accelerated ESCC cell migration and invasion and decreased ESCC cell apoptosis via the Bax/Bcl‑2 pathway and cleaved caspase‑3. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was detected as a target of miR‑92a‑3p by a dual luciferase reporter assay. The overexpression of PTEN not only inhibited ESCC proliferation, migration and invasion, but also promoted ESCC cell apoptosis. PTEN and the miR‑92a‑3p mimic inhibited and promoted ESCC proliferation, respectively, which may be associated with the PI3K/Akt pathway. The results of the study revealed that miR‑92a‑3p promoted the proliferation, migration and invasion of ESCC, and the effect of miR‑92a‑3p on ESCC was realized by regulating PTEN.

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1	Enzinger PC and Mayer RJ: Esophageal cancer. N Engl J Med. 349:2241–2252. 2003. View Article : Google Scholar : PubMed/NCBI
2	Short MW, Burgers KG and Fry VT: Esophageal cancer. Am Fam Physician. 95:22–28. 2017.PubMed/NCBI
3	Daly JM, Fry WA, Little AG, Winchester DP, McKee RF, Stewart AK and Fremgen AM: Esophageal cancer: Results of an American college of surgeons patient care evaluation study. J Am Coll Surg. 190:562–563. 2000. View Article : Google Scholar : PubMed/NCBI
4	Siewert JR, Stein HJ, Feith M, Bruecher BL, Bartels H and Fink U: Histologic tumor type is an independent prognostic parameter in esophageal cancer: Lessons from more than 1,000 consecutive resections at a single center in the Western world. Ann Surg. 234:360–369. 2001. View Article : Google Scholar : PubMed/NCBI
5	Rice TW, Apperson-Hansen C, DiPaola LM, Semple ME, Lerut TE, Orringer MB, Chen LQ, Hofstetter WL, Smithers BM, Rusch VW, et al: Worldwide esophageal cancer collaboration: Clinical staging data. Dis Esophagus. 29:707–714. 2016. View Article : Google Scholar : PubMed/NCBI
6	Kaz AM and Grady WM: Epigenetic biomarkers in esophageal cancer. Cancer Lett. 342:193–199. 2014. View Article : Google Scholar
7	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
8	Cui J, Zhou B, Ross SA and Zempleni J: Nutrition, microRNAs, and human health. Adv Nutr. 8:105–112. 2017. View Article : Google Scholar : PubMed/NCBI
9	Hayes J, Peruzzi PP and Lawler S: MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med. 20:460–469. 2014. View Article : Google Scholar : PubMed/NCBI
10	Di Leva G, Garofalo M and Croce CM: MicroRNAs in cancer. Annu Rev Pathol. 9:287–314. 2014. View Article : Google Scholar :
11	Feng QQ, Dong ZQ, Zhou Y, Zhang H and Long C: miR-16-1-3 ptargets TWIST1 to inhibit cell proliferation and invasion in NSCLC. Bratisl Lek Listy. 119:60–65. 2018.
12	Li H, Bian C, Liao L, Li J and Zhao RC: miR-17-5p promotes human breast cancer cell migration and invasion through suppression of HBP1. Breast Cancer Res Treat. 126:565–575. 2011. View Article : Google Scholar
13	Cun J and Yang Q: Bioinformatics-based interaction analysis of miR-92a-3p and key genes in tamoxifen-resistant breast cancer cells. Biomed Pharmacother. 107:117–128. 2018. View Article : Google Scholar : PubMed/NCBI
14	Ke TW, Wei PL, Yeh KT, Chen WT and Cheng YW: miR-92a promotes cell metastasis of colorectal cancer through PTEN-Mediated PI3K/AKT pathway. Ann Surg Oncol. 22:2649–2655. 2015. View Article : Google Scholar
15	Shen Y, Ding Y, Ma Q, Zhao L, Guo X, Shao Y, Niu C, He Y, Zhang F, Zheng D, et al: Identification of novel circulating MicroRNA biomarkers for the diagnosis of esophageal squamous cell carcinoma and squamous dysplasia. Cancer Epidemiol Biomarkers Prev. Apr 15–2019, Epub ahead of print. View Article : Google Scholar
16	Liu MX, Liao J, Xie M, Gao ZK, Wang XH, Zhang Y, Shang MH, Yin LH, Pu YP and Liu R: miR-93-5p transferred by exosomes promotes the proliferation of esophageal cancer cells via inter-cellular communication by targeting PTEN. Biomed Environ Sci. 31:171–185. 2018.PubMed/NCBI
17	Tullius BP, Shankar SP, Cole S, Triano V, Aradhya S, Huang EC, Sanchez T and Pawar A: Novel heterozygous mutation in the PTEN gene associated with ovarian germ cell tumor complicated by growing teratoma syndrome and overgrowth in a two-year-old female. Pediatr Blood Cancer. e277882019. View Article : Google Scholar : PubMed/NCBI
18	Yan Y, Li Z, Zeng S, Wang X, Gong Z and Xu Z: FGFR2-mediated phosphorylation of PTEN at tyrosine 240 contributes to the radioresistance of glioma. J Cell Commun Signal. Apr 25–2019, Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
19	Zhao MY, Wang LM, Liu J, Huang X, Liu J and Zhang YF: miR-21 Suppresses Anoikis through targeting PDCD4 and PTEN in human esophageal adenocarcinoma. Curr Med Sci. 38:245–251. 2018. View Article : Google Scholar : PubMed/NCBI
20	Tutar L, Tutar E and Tutar Y: MicroRNAs and cancer; an overview. Curr Pharm Biotechnol. 15:430–437. 2014. View Article : Google Scholar : PubMed/NCBI
21	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
22	Jacobson MD, Weil M and Raff MC: Programmed cell death in animal development. Cell. 88:347–354. 1997. View Article : Google Scholar : PubMed/NCBI
23	Fuchs Y and Steller H: Programmed cell death in animal development and disease. Cell. 147:742–758. 2011. View Article : Google Scholar : PubMed/NCBI
24	Kerr JF, Wyllie AH and Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI
25	Tang HL, Tang HM, Mak KH, Hu S, Wang SS, Wong KM, Wong CS, Wu HY, Law HT, Liu K, et al: Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response. Mol Biol Cell. 23:2240–2252. 2012. View Article : Google Scholar : PubMed/NCBI
26	Joshi GN and Knecht DA: Multi-parametric analysis of cell death pathways using live-cell microscopy. Curr Protoc Toxicol. 58:Unit 4.40. 2013. View Article : Google Scholar
27	Dietrich JB: Apoptosis and anti-apoptosis genes in the Bcl-2 family. Arch Physiol Biochem. 105:125–135. 1997.In French. View Article : Google Scholar : PubMed/NCBI
28	Kvansakul M, Caria S and Hinds MG: The Bcl-2 family in Host-Virus interactions. Viruses. 9:E2902017. View Article : Google Scholar : PubMed/NCBI
29	Crowley LC and Waterhouse NJ: Detecting cleaved caspase-3 in apoptotic cells by flow cytometry. Cold Spring Harbor Protocols. Nov 1–2016, Epub ahead of print. View Article : Google Scholar
30	Han T, Kang D, Ji D, Wang X, Zhan W, Fu M, Xin HB and Wang JB: How does cancer cell metabolism affect tumor migration and invasion? Cell Adh Migr. 7:395–403. 2013. View Article : Google Scholar : PubMed/NCBI
31	Chambers AF, Groom AC and MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2:563–572. 2002. View Article : Google Scholar : PubMed/NCBI
32	Duff D and Long A: Roles for RACK1 in cancer cell migration and invasion. Cell Signal. 35:250–255. 2017. View Article : Google Scholar : PubMed/NCBI
33	Tungsukruthai S, Sritularak B and Chanvorachote P: Cycloarto-biloxanthone inhibits migration and invasion of lung cancer cells. Anticancer Res. 37:6311–6319. 2017.PubMed/NCBI
34	Yang X, Xu Y, Wang T, Shu D, Guo P, Miskimins K and Qian SY: Inhibition of cancer migration and invasion by knocking down delta-5-desaturase in COX-2 overexpressed cancer cells. Redox Biol. 11:653–662. 2017. View Article : Google Scholar : PubMed/NCBI
35	Zhang N, Fu H, Song L, Ding Y, Wang X, Zhao C and Zhao Y, Jiao F and Zhao Y: MicroRNA-100 promotes migration and invasion through mammalian target of rapamycin in esophageal squamous cell carcinoma. Oncol Rep. 32:1409–1418. 2014. View Article : Google Scholar : PubMed/NCBI
36	Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 275:1943–1947. 1997. View Article : Google Scholar : PubMed/NCBI
37	Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, et al: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 15:356–362. 1997. View Article : Google Scholar : PubMed/NCBI
38	Malaney P, Uversky VN and Davé V: PTEN proteoforms in biology and disease. Cell Mol Life Sci. 74:2783–2794. 2017. View Article : Google Scholar : PubMed/NCBI
39	Guo H, German P, Bai S, Barnes S, Guo W, Qi X, Lou H, Liang J, Jonasch E, Mills GB and Ding Z: The PI3K/AKT pathway and renal cell carcinoma. J Genet Genomics. 42:343–353. 2015. View Article : Google Scholar : PubMed/NCBI
40	Chen H, Zhou L, Wu X, Li R, Wen J, Sha J and Wen X: The PI3K/AKT pathway in the pathogenesis of prostate cancer. Front Biosci (Landmark Ed). 21:1084–1091. 2016. View Article : Google Scholar
41	Mayer IA and Arteaga CL: The PI3K/AKT pathway as a target for cancer treatment. Annu Rev Med. 67:11–28. 2016. View Article : Google Scholar
42	Yu M, Wang H, Xu Y, Yu D, Li D, Liu X and Du W: Insulin-like growth factor-1 (IGF-1) promotes myoblast proliferation and skeletal muscle growth of embryonic chickens via the PI3K/Akt signalling pathway. Cell Biol Int. 39:910–922. 2015. View Article : Google Scholar : PubMed/NCBI