Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

Liu,Yi; Salai,Adili; He,Dan; Gao,Shengli; Zeng,Wei

doi:10.3892/etm.2019.7940

Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

Authors:
- Yi Liu
- Adili Salai
- Dan He
- Shengli Gao
- Wei Zeng
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Affiliations: Department of Cardiothoracic Surgery, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, P.R. China, Department of Thoracic Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, P.R. China
Published online on: August 26, 2019 https://doi.org/10.3892/etm.2019.7940
Pages: 3622-3630

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Abstract

MicroRNA (miR)‑10b is highly expressed in esophageal cancer tissues and is associated with poor prognosis of esophageal cancer. However, the role and mechanism of miR‑10b in esophageal cancer cells remains unclear, therefore, the present study aimed to investigate this. Esophageal cancer cells, TE‑1 and EC9706, were transfected with miR‑10b mimic, miR‑10b inhibitor or incubated with transforming growth factor‑β (TGF‑β). MTT and EdU assays were used to detect cell proliferation. Flow cytometry was used to determine cell cycle analysis and apoptosis. Cell migration and invasion were also analyzed. Western blot analysis was used to detect protein levels and reverse transcription‑quantitative PCR was used to analyze miR‑10b expression. The present results demonstrated that, compared with the control group, miR‑10b significantly promoted TE‑1 and EC9706 cell proliferation. Compared with miR‑10b inhibitor group and control group, miR‑10b mimic promoted esophageal cancer cell cycle progression, inhibited apoptosis of esophageal cancer cells and promoted the migration and invasion of cells. The proliferation of esophageal cancer cells increased in a dose‑dependent manner with TGF‑β concentration. TGF‑β treatment induced high expression of miR‑10b in both cell lines. The miR‑10b mimic + TGF‑β group further promoted the migration and invasion of esophageal cancer cells. Western blot analysis determined that, compared with the control group, miR‑10b mimic increased TGF‑β expression. miR‑10b mimic also inhibited the expression of phosphatase and tensin homolog (PTEN) in tumor cells. Compared with the control group, TGF‑β inhibited the expression of PTEN with the miR‑10b mimic + TGF‑β group further inhibiting the PTEN. miR‑10b inhibitor + TGF‑β reversed the effect of TGF‑β and miR‑10b on PTEN. In conclusion, miR‑10b promoted cell cycle progression, inhibited apoptosis and promoted the migration and invasion of esophageal cancer cells. The mechanism may be related to the upregulation of TGF‑β and the downregulation of PTEN. The present findings suggested that miR‑10b might be a potential therapeutic target for esophageal cancer.

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1	Stappert L, Roese-Koerner B and Brustle O: The role of microRNAs in human neural stem cells, neuronal differentiation and subtype specification. Cell Tissue Res. 359:47–64. 2015. View Article : Google Scholar : PubMed/NCBI
2	Villegas-Ruiz V, Juárez-Méndez S, Pérez-González OA, Arreola H, Paniagua-García L, Parra-Melquiadez M, Peralta-Rodríguez R, López-Romero R, Monroy-García A, Mantilla-Morales A, et al: Heterogeneity of microRNAs expression in cervical cancer cells: Over-expression of miR-196a. Int J Clin Exp Pathol. 7:1389–1401. 2014.PubMed/NCBI
3	Ye JJ and Cao J: MicroRNAs in colorectal cancer as markers and targets: Recent advances. World J Gastroenterol. 20:4288–4299. 2014. View Article : Google Scholar : PubMed/NCBI
4	He B, Yin B, Wang B, Xia Z, Chen C and Tang J: MicroRNAs in esophageal cancer (review). Mol Med Rep. 6:459–465. 2012.PubMed/NCBI
5	Ahmad A, Ginnebaugh KR, Yin S, Bollig-Fischer A, Reddy KB and Sarkar FH: Functional role of miR-10b in tamoxifen resistance of ER-positive breast cancer cells through down-regulation of HDAC4. BMC Cancer. 15:5402015. View Article : Google Scholar : PubMed/NCBI
6	Knirsh R, Ben-Dror I, Modai S, Shomron N and Vardimon L: MicroRNA 10b promotes abnormal expression of the proto-oncogene c-Jun in metastatic breast cancer cells. Oncotarget. 7:59932–59944. 2016. View Article : Google Scholar : PubMed/NCBI
7	Zhen L, Li J, Zhang M and Yang K: MiR-10b decreases sensitivity of glioblastoma cells to radiation by targeting AKT. J Biol Res (Thessalon). 23:142016. View Article : Google Scholar : PubMed/NCBI
8	Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI
9	Short MW, Burgers KG and Fry VT: Esophageal cancer. Am Fam Physician. 95:22–28. 2017.PubMed/NCBI
10	Lin Y, Totsuka Y, Shan B, Wang C, Wei W, Qiao Y, Kikuchi S, Inoue M, Tanaka H and He Y: Esophageal cancer in high-risk areas of China: Research progress and challenges. Ann Epidemiol. 27:215–221. 2017. View Article : Google Scholar : PubMed/NCBI
11	Xu H, Yao Y, Meng F, Qian X, Jiang X, Li X, Gao Z and Gao L: Predictive value of serum miR-10b, miR-29c, and miR-205 as promising biomarkers in esophageal squamous cell carcinoma screening. Medicine (Baltimore). 94:e15582015. View Article : Google Scholar : PubMed/NCBI
12	Massagué J: TGFbeta in cancer. Cell. 134:215–230. 2008. View Article : Google Scholar : PubMed/NCBI
13	Mishra L, Derynck R and Mishra B: Transforming growth factor-beta signaling in stem cells and cancer. Science. 310:68–71. 2005. View Article : Google Scholar : PubMed/NCBI
14	Madhunapantula SV and Robertson GP: The PTEN-AKT3 signaling cascade as a therapeutic target in melanoma. Pigment Cell Melanoma Res. 22:400–419. 2010. View Article : Google Scholar
15	Georgescu MM: PTEN tumor suppressor Network in PI3K-Akt pathway control. Genes Cancer. 1:1170–1177. 2010. View Article : Google Scholar : PubMed/NCBI
16	Jamali L, Tofigh R, Tutunchi S, Panahi G, Borhani F, Akhavan S, Nourmohammadi P, Ghaderian SMH, Rasouli M and Mirzaei H: Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers. J Cell Physiol. 233:8538–8550. 2018. View Article : Google Scholar : PubMed/NCBI
17	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 Dec. 25:402–408. 2001. View Article : Google Scholar
18	Xu W, Yang Z, Zhou SF and Lu N: Posttranslational regulation of phosphatase and tensin homolog (PTEN) and its functional impact on cancer behaviors. Drug Des Devel Ther. 8:1745–1751. 2014. View Article : Google Scholar : PubMed/NCBI
19	Bahena-Ocampo I, Espinosa M, Ceballos-Cancino G, Lizarraga F, Campos-Arroyo D, Schwarz A, Garcia-Lopez P, Maldonado V and Melendez-Zajgla J: miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation. EMBO Rep. 17:10812016. View Article : Google Scholar : PubMed/NCBI
20	Wang W: Study of miR-10b regulatory mechanism for epithelial-mesenchymal transition, invasion and migration in nasopharyngeal carcinoma cells. Oncol Lett. 14:7207–7210. 2017.PubMed/NCBI
21	Zhang Y, Liao RB, Hu LL, Tong BX, Hao TF and Wu HJ: The microRNA miR-10b as a potentially promising biomarker to predict the prognosis of cancer patients: A meta-analysis. Oncotarget. 8:104543–104551. 2017.PubMed/NCBI
22	Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H and Liu Z: MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 285:7986–7994. 2010. View Article : Google Scholar : PubMed/NCBI
23	Carlsson J, Christiansen J, Davidsson S, Giunchi F, Fiorentino M and Sundqvist P: The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma. Oncol Lett. 17:4566–4574. 2019.PubMed/NCBI
24	Zhang J, Yang J, Zhang X, Xu J, Sun Y and Zhang P: MicroRNA-10b expression in breast cancer and its clinical association. PLoS One. 13:e01925092018. View Article : Google Scholar : PubMed/NCBI
25	Hujie G, Zhou SH, Zhang H, Qu J, Xiong XW, Hujie O, Liao CG and Yang SE: MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma. Cancer Cell Int. 18:102018. View Article : Google Scholar : PubMed/NCBI
26	Moustakas A and Heldin CH: The regulation of TGFbeta signal transduction. Development. 136:3699–3714. 2009. View Article : Google Scholar : PubMed/NCBI
27	Pickup M, Novitskiy S and Moses HL: The roles of TGF beta in the tumour microenvironment. Nat Rev Cancer. 13:788–799. 2013. View Article : Google Scholar : PubMed/NCBI
28	Zheng T and Yang J: Mechanism of transforming growth factor β in patients with hepatocellular carcinoma. Chin J Hepatobiliary Surg. 6:425–428. 2016.
29	He Z, Dong W, Li Q, Qin C and Li Y: Sauchinone prevents TGF-β-induced EMT and metastasis in gastric cancer cells. Biomed Pharmacother. 101:355–361. 2018. View Article : Google Scholar : PubMed/NCBI
30	Katsuno Y, Lamouille S and Derynck R: TGF-beta signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 25:76–84. 2013. View Article : Google Scholar : PubMed/NCBI
31	Ma C, Wei F, Xia H, Liu H, Dong X, Zhang Y, Luo Q, Liu Y and Li Y: MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition. Int J Oncol. 50:1739–1748. 2017. View Article : Google Scholar : PubMed/NCBI
32	Ouyang H, Gore J, Deitz S and Korc M: MicroRNA-10b enhances pancreatic cancer cell invasion by suppressing TIP30 expression and promoting EGF and TGF-beta actions. Oncogene. 36:49522017. View Article : Google Scholar : PubMed/NCBI
33	Zhong H, Wang HR, Yang S, Zhong JH, Wang T, Wang C and Chen FY: Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line. Int J Hematol. 92:129–135. 2010. View Article : Google Scholar : PubMed/NCBI
34	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 intercellular communication by targeting PTEN. Biomed Environ Sci. 31:171–185. 2018.PubMed/NCBI
35	Liang HX, Sun LB and Liu NJ: Neferine inhibits proliferation, migration and invasion of U251 glioma cells by down-regulation of miR-10b. Biomed Pharmacother. 109:1032–1040. 2019. View Article : Google Scholar : PubMed/NCBI