Overexpression of microRNA‑1470 promotes proliferation and migration, and inhibits senescence of esophageal squamous carcinoma cells

Mei,Li‑Li; Qiu,Yun‑Tan; Wang,Wen‑Jun; Bai,Jie; Shi,Zhi‑Zhou

doi:10.3892/ol.2017.7190

Overexpression of microRNA‑1470 promotes proliferation and migration, and inhibits senescence of esophageal squamous carcinoma cells

Authors:
- Li‑Li Mei
- Yun‑Tan Qiu
- Wen‑Jun Wang
- Jie Bai
- Zhi‑Zhou Shi
View Affiliations

Affiliations: Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
Published online on: October 16, 2017 https://doi.org/10.3892/ol.2017.7190
Pages: 7753-7758
Copyright: © Mei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

MicroRNA‑1470 (miR‑1470) is overexpressed in esophageal squamous cell carcinoma (ESCC); however, its role and underlying molecular mechanism remain unknown. The aim of the present study was to explore the tumorigenic role and mechanism of miR‑1470 overexpression in ESCC. The expression of miR‑1470 in ESCC tissues and cell lines was detected using human miRNA microarrays and the reverse transcription‑quantitative polymerase chain reaction, respectively. The effects of miR‑1470 on cell proliferation, migration and senescence were determined using a Cell Counting Kit‑8 assay, Transwell migration assay and β‑galactosidase staining kit. Western blotting was used to analyze the expression levels of genes in the apoptosis signaling pathway. An increased expression level of miR‑1470 was observed in ESCC tissues compared with that in paracancerous tissues. Knockdown of miR‑1470 significantly suppressed proliferation, and down‑regulated the cell cycle regulatory gene cyclin E1. It was also revealed that knockdown of miR‑1470 significantly inhibited migration, and decreased the expression levels of matrix metalloproteinase 2 (MMP2), MMP13 and MMP14. Western blotting analysis revealed that knockdown of miR‑1470 induced apoptosis by increasing B‑cell lymphoma 2 (Bcl‑2) expression. The results of the present study suggest that overexpression of miR‑1470 in ESCC promotes cancer cell proliferation by accelerating the cell cycle and inhibiting apoptosis, and also enhances cancer cell migration by upregulating MMPs.

View Figures

View References

1	Zhao P, Dai M, Chen W and Li N: Cancer trends in China. Jpn J Clin Oncol. 40:281–285. 2010. View Article : Google Scholar : PubMed/NCBI
2	Mariette C, Piessen G and Triboulet JP: Therapeutic strategies in oesophageal carcinoma: Role of surgery and other modalities. Lancet Oncol. 8:545–553. 2007. View Article : Google Scholar : PubMed/NCBI
3	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
4	Ell C and Lorenz D: Diagnosis and treatment of oesophageal carcinoma: Changes in every respect. Viszeralmedizin. 31:3142015.PubMed/NCBI
5	Acunzo M and Croce CM: MicroRNA in Cancer and Cachexia-A Mini-Review. J Infect Dis. 212 Suppl 1:S74–S77. 2015. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Iorio MV and Croce CM: MicroRNAs in cancer: Small molecules with a huge impact. J Clin Oncol. 27:5848–5856. 2009. View Article : Google Scholar : PubMed/NCBI
8	Li S, Qin X, Li Y, Zhang X, Niu R, Zhang H, Cui A, An W and Wang X: MiR-133a suppresses the migration and invasion of esophageal cancer cells by targeting the EMT regulator SOX4. Am J Transl Res. 7:1390–1403. 2015.PubMed/NCBI
9	Mao Y, Li L, Liu J, Wang L and Zhou Y: MiR-495 inhibits esophageal squamous cell carcinoma progression by targeting Akt1. Oncotarget. 7:51223–51236. 2016. View Article : Google Scholar : PubMed/NCBI
10	Llambi F and Green DR: Apoptosis and oncogenesis: Give and take in the BCL-2 family. Curr Opin Genet Dev. 21:12–20. 2011. View Article : Google Scholar : PubMed/NCBI
11	Fulda S, Meyer E and Debatin KM: Inhibition of TRAIL-induced apoptosis by Bcl-2 overexpression. Oncogene. 21:2283–2294. 2002. View Article : Google Scholar : PubMed/NCBI
12	Thoms HC, Dunlop MG and Stark LA: p38-mediated inactivation of cyclin D1/cyclin-dependent kinase 4 stimulates nucleolar translocation of RelA and apoptosis in colorectal cancer cells. Cancer Res. 67:1660–1669. 2007. View Article : Google Scholar : PubMed/NCBI
13	Törmänen-Näpänkangas U, Soini Y, Kahlos K, Kinnula V and Pääkkö P: Expression of caspases-3, −6 and −8 and their relation to apoptosis in non-small cell lung carcinoma. Int J Cancer. 93:192–198. 2001. View Article : Google Scholar : PubMed/NCBI
14	Li YH, Wang C, Meng K, Chen LB and Zhou XJ: Influence of survivin and caspase-3 on cell apoptosis and prognosis in gastric carcinoma. World J Gastroenterol. 10:1984–1988. 2004. View Article : Google Scholar : PubMed/NCBI
15	Li SX, Chai L, Cai ZG, Jin LJ, Chen Y, Wu HR and Sun Z: Expression of survivin and caspase 3 in oral squamous cell carcinoma and peritumoral tissue. Asian Pac J Cancer Prev. 13:5027–5031. 2012. View Article : Google Scholar : PubMed/NCBI
16	Nassar A, Lawson D, Cotsonis G and Cohen C: Survivin and caspase-3 expression in breast cancer: Correlation with prognostic parameters, proliferation, angiogenesis, and outcome. Appl Immunohistochem Mol Morphol. 16:113–120. 2008. View Article : Google Scholar : PubMed/NCBI
17	Hsia JY, Chen CY, Chen JT, Hsu CP, Shai SE, Yang SS, Chuang CY, Wang PY and Miaw J: Prognostic significance of caspase-3 expression in primary resected esophageal squamous cell carcinoma. Eur J Surg Oncol. 29:44–48. 2003. View Article : Google Scholar : PubMed/NCBI
18	Chen J, Yang H, Wen J, Luo K, Liu Q, Huang Y, Zheng Y, Tan Z, Huang Q and Fu J: NHE9 induces chemoradiotherapy resistance in esophageal squamous cell carcinoma by upregulating the Src/Akt/β-catenin pathway and Bcl-2 expression. Oncotarget. 6:12405–12420. 2015. View Article : Google Scholar : PubMed/NCBI
19	Hendrickson AW, Meng XW and Kaufmann SH: Anticancer therapy: Boosting the bang of Bim. J Clin Invest. 118:3582–3584. 2008. View Article : Google Scholar : PubMed/NCBI
20	Youle RJ and Strasser A: The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 9:47–59. 2008. View Article : Google Scholar : PubMed/NCBI
21	Stauber RH, Mann W and Knauer SK: Nuclear and cytoplasmic survivin: Molecular mechanism, prognostic, and therapeutic potential. Cancer Res. 67:5999–6002. 2007. View Article : Google Scholar : PubMed/NCBI
22	Zhang X, Wang C, Shan S, Liu X, Jiang Z and Ren T: TLR4/ROS/miRNA-21 pathway underlies lipopolysaccharide instructed primary tumor outgrowth in lung cancer patients. Oncotarget. 7:42172–42182. 2016. View Article : Google Scholar : PubMed/NCBI
23	Xicola RM, Bontu S, Doyle BJ, Rawson J, Garre P, Lee E, de la Hoya M, Bessa X, Clofent J, Bujanda L, et al: Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC). Carcinogenesis. 37:751–758. 2016. View Article : Google Scholar : PubMed/NCBI
24	Bimonte S, Leongito M, Barbieri A, Del Vecchio V, Falco M, Giudice A, Palaia R, Albino V, Di Giacomo R, Petrillo A, et al: The therapeutic targets of miRNA in hepatic cancer stem cells. Stem Cells Int. 2016:10652302016. View Article : Google Scholar : PubMed/NCBI
25	Wu BL, Xu LY, Du ZP, Liao LD, Zhang HF, Huang Q, Fang GQ and Li EM: MiRNA profile in esophageal squamous cell carcinoma: Downregulation of miR-143 and miR-145. World J Gastroenterol. 17:79–88. 2011. View Article : Google Scholar : PubMed/NCBI
26	Chen Z, Li J, Tian L, Zhou C, Gao Y, Zhou F, Shi S, Feng X, Sun N, Yao R, et al: MiRNA expression profile reveals a prognostic signature for esophageal squamous cell carcinoma. Cancer Lett. 350:34–42. 2014. View Article : Google Scholar : PubMed/NCBI
27	Kong KL, Kwong DL, Chan TH, Law SY, Chen L, Li Y, Qin YR and Guan XY: MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut. 61:33–42. 2012. View Article : Google Scholar : PubMed/NCBI
28	Winther M, Alsner J, Tramm T, Baeksgaard L, Holtved E and Nordsmark M: Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer. Acta Oncol. 54:1582–1591. 2015. View Article : Google Scholar : PubMed/NCBI
29	Cui XB, Li S, Li TT, Peng H, Jin TT, Zhang SM, Liu CX, Yang L, Shen YY, Li SG, et al: Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma. Oncotarget. 7:1777–1795. 2016. View Article : Google Scholar : PubMed/NCBI
30	Nie W, Song W, Zhang W, Wang Y, Zhu A, Shao J and Guan X: miR-1470 mediates lapatinib induced p27 upregulation by targeting c-jun. J Cell Physiol. 230:1630–1639. 2015. View Article : Google Scholar : PubMed/NCBI
31	Banday MZ, Sameer AS, Mir AH, Mokhdomi TA, Chowdri NA and Haq E: Matrix metalloproteinase (MMP)-2, −7 and −9 promoter polymorphisms in colorectal cancer in ethnic Kashmiri population-A case-control study and a mini review. Gene. 589:81–89. 2016. View Article : Google Scholar : PubMed/NCBI
32	Serra R, Grande R, Gallelli L, Rende P, Scarcello E, Buffone G, Caliò FG, Gasbarro V, Amato B and de Franciscis S: Carotid body paragangliomas and matrix metalloproteinases. Ann Vasc Surg. 28:1665–1670. 2014. View Article : Google Scholar : PubMed/NCBI
33	Muñoz-Espín D and Serrano M: Cellular senescence: From physiology to pathology. Nat Rev Mol Cell Biol. 15:482–496. 2014. View Article : Google Scholar : PubMed/NCBI