miR‑215 functions as a tumor suppressor and directly targets ZEB2 in human non‑small cell lung cancer Retraction in /10.3892/ol.2021.12861

Hou,Yan; Zhen,Junwen; Xu,Xiaodong; Zhen,Kun; Zhu,Bin; Pan,Rui; Zhao,Chidong

doi:10.3892/ol.2015.3587

miR‑215 functions as a tumor suppressor and directly targets ZEB2 in human non‑small cell lung cancer

Retraction in: /10.3892/ol.2021.12861

Authors:
- Yan Hou
- Junwen Zhen
- Xiaodong Xu
- Kun Zhen
- Bin Zhu
- Rui Pan
- Chidong Zhao
View Affiliations

Affiliations: Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Pediatrics, Central Hospital, Xiangyang, Hubei 441021, P.R. China
Published online on: August 11, 2015 https://doi.org/10.3892/ol.2015.3587
Pages: 1985-1992
Copyright: © Hou 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‑215 (miR‑215) has previously been demonstrated to be dysregulated in a number of human malignancies and to be correlated with tumor progression. However, the expression and function of miR‑215 in non‑small cell lung cancer (NSCLC) has remained to be elucidated. Therefore, the present study aimed to investigate the effects of miR‑215 in NSCLC tumorigenesis and development. Reverse transcription‑quantitative polymerase chain reaction was used to evaluate miR‑215 expression in NSCLC cell lines and primary tumor tissues. The association between miR‑215 expression and certain clinicopathological factors was also determined, and the effects of miR‑215 on the biological behavior of NSCLC cells were investigated. In addition, the potential regulatory function of miR‑215 on zinc finger E‑box‑binding homeobox 2 (ZEB2) expression was examined. miR‑215 expression was significantly downregulated in NSCLC cell lines and clinical specimens. Reduced miR‑215 expression was significantly associated with lymph node metastasis and advanced TNM stage. Overexpression of miR‑215 inhibited NSCLC cell proliferation, invasion and migration, and promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. Furthermore, luciferase reporter assay analysis identified ZEB2 as a direct target of miR‑215. These findings indicated that miR‑215 may act as a tumor suppressor in NSCLC and may serve as a novel therapeutic agent for miR‑based therapy.

View Figures

View References

1	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C and Thun MJ: Cancer statistics, 2006. CA Cancer J Clin. 56:106–130. 2006. View Article : Google Scholar : PubMed/NCBI
3	Ma Q, Jiang Q, Pu Q, Zhang X, Yang W, Wang Y, Ye S, Wu S, Zhong G, Ren J, et al: MicroRNA-143 inhibits migration and invasion of human non-small-cell lung cancer and its relative mechanism. Int J Biol Sci. 9:680–692. 2013. View Article : Google Scholar : PubMed/NCBI
4	Yin LG, Zou ZQ, Zhao HY, Zhang CL, Shen JG, Qi L, Qi M and Xue ZQ: Analysis of tissue-specific differentially methylated genes with differential gene expression in non-small cell lung cancer. Mol Biol (Mosk). 48:797–804. 2014.(In Russian). View Article : Google Scholar : PubMed/NCBI
5	Zhao X, Zhang Z, Yuan Y and Yuan X: Polymorphisms in ERCC1 gene could predict clinical outcome of platinum-based chemotherapy for non-small cell lung cancer patients. Tumour Biol. 35:8335–8341. 2014. View Article : Google Scholar : PubMed/NCBI
6	Yoo SS, Lee SM, Do SK, Lee WK, Kim DS and Park JY: Unmethylation of the CHRNB4 gene is an unfavorable prognostic factor in non-small cell lung cancer. Lung Cancer. 86:85–90. 2014. View Article : Google Scholar : PubMed/NCBI
7	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
8	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
9	Heneghan HM, Miller N and Kerin MJ: MiRNAs as biomarkers and therapeutic targets in cancer. Curr Opin Pharmacol. 10:543–550. 2010. View Article : Google Scholar : PubMed/NCBI
10	Liang H, Li Y, Luo RY and Shen FJ: MicroRNA-215 is a potential prognostic marker for cervical cancer. J Huazhong Univ Sci Technolog Med Sci. 34:207–212. 2014. View Article : Google Scholar : PubMed/NCBI
11	Liu F, You X, Chi X, Wang T, Ye L, Niu J and Zhang X: Hepatitis B virus X protein mutant HBxΔ127 promotes proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT. Biochem Biophys Res Commun. 444:128–134. 2014. View Article : Google Scholar : PubMed/NCBI
12	Deng Y, Huang Z, Xu Y, et al: MiR-215 modulates gastric cancer cell proliferation by targeting RB1. Cancer Lett. 342:27–35. 2014. View Article : Google Scholar : PubMed/NCBI
13	Walter BA, Valera VA, Pinto PA and Merino MJ: Comprehensive microRNA profiling of prostate cancer. J Cancer. 4:350–357. 2013. View Article : Google Scholar : PubMed/NCBI
14	Wijnhoven BP, Hussey DJ, Watson DI, Tsykin A, Smith CM and Michael MZ: South Australian Oesophageal Research Group: MicroRNA profiling of Barrett's oesophagus and oesophageal adenocarcinoma. Br J Surg. 97:853–861. 2010. View Article : Google Scholar : PubMed/NCBI
15	Karaayvaz M, Pal T, Song B, et al: Prognostic significance of miR-215 in colon cancer. Clin Colorectal Cancer. 10:340–347. 2011. View Article : Google Scholar : PubMed/NCBI
16	White NM, Khella HW, Grigull J, et al: miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215. Br J Cancer. 105:1741–1749. 2011. View Article : Google Scholar : PubMed/NCBI
17	De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI
18	Comijn J, Berx G, Vermassen P, et al: The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 7:1267–1278. 2001. View Article : Google Scholar : PubMed/NCBI
19	Usova EV, Kopantseva MR, Kostina MB, Vankovich AN, Egorov VI and Kopantsev EP: Expression of the ZEB2 gene in pancreatic stromal cells in pancreatic ductal adenocarcinoma, pancreatitis, and normal state. Dokl Biol Sci. 448:61–64. 2013. View Article : Google Scholar : PubMed/NCBI
20	Fang Y, Wei J, Cao J, et al: Protein expression of ZEB2 in renal cell carcinoma and its prognostic significance in patient survival. PLoS One. 8:e625582013. View Article : Google Scholar : PubMed/NCBI
21	Lee H, Jun SY, Lee YS, Lee HJ, Lee WS and Park CS: Expression of miRNAs and ZEB1 and ZEB2 correlates with histopathological grade in papillary urothelial tumors of the urinary bladder. Virchows Arch. 464:213–220. 2014. View Article : Google Scholar : PubMed/NCBI
22	Fang S, Zeng X, Zhu W, Tang R, Chao Y and Guo L: Zinc finger E-box-binding homeobox 2 (ZEB2) regulated by miR-200b contributes to multi-drug resistance of small cell lung cancer. Exp Mol Pathol. 96:438–444. 2014. View Article : Google Scholar : PubMed/NCBI
23	You J, Li Y, Fang N, et al: MiR-132 suppresses the migration and invasion of lung cancer cells via targeting the EMT regulator ZEB2. PLoS One. 9:e918272014. View Article : Google Scholar : PubMed/NCBI
24	Zheng YB, Luo HP, Shi Q, et al: miR-132 inhibits colorectal cancer invasion and metastasis via directly targeting ZEB2. World J Gastroenterol. 20:6515–6522. 2014. View Article : Google Scholar : PubMed/NCBI
25	Guan H, Liang W, Xie Z, et al: Down-regulation of miR-144 promotes thyroid cancer cell invasion by targeting ZEB1 and ZEB2. Endocrine. 48:566–574. 2015. View Article : Google Scholar : PubMed/NCBI
26	Lu YM, Shang C, Ou YL, et al: miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc finger E-box-binding homeobox 2 (ZEB2) expression. Med Oncol. 31:1342014. View Article : Google Scholar : PubMed/NCBI
27	Chiang Y, Song Y, Wang Z, et al: microRNA-192, -194 and -215 are frequently downregulated in colorectal cancer. Exp Ther Med. 3:560–566. 2012.PubMed/NCBI
28	Li S, Gao J, Gu J, Yuan J, Hua D and Shen L: MicroRNA-215 inhibits relapse of colorectal cancer patients following radical surgery. Med Oncol. 30:5492013. View Article : Google Scholar : PubMed/NCBI
29	Song B, Wang Y, Titmus MA, Botchkina G, Formentini A, Kornmann M and Ju J: Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer. 9:962010. View Article : Google Scholar : PubMed/NCBI
30	Liu GF, Tang D, Li P, et al: S-1-based combination therapy vs S-1 monotherapy in advanced gastric cancer: A meta-analysis. World J Gastroenterol. 20:310–318. 2014. View Article : Google Scholar : PubMed/NCBI
31	Jin Z, Selaru FM, Cheng Y, et al: MicroRNA-192 and -215 are upregulated in human gastric cancer in vivo and suppress ALCAM expression in vitro. Oncogene. 30:1577–1585. 2011. View Article : Google Scholar : PubMed/NCBI
32	Senanayake U, Das S, Vesely P, et al: miR-192, miR-194, miR-215, miR-200c and miR-141 are downregulated and their common target ACVR2B is strongly expressed in renal childhood neoplasms. Carcinogenesis. 33:1014–1021. 2012. View Article : Google Scholar : PubMed/NCBI
33	Brennecke J, Stark A, Russell RB and Cohen SM: Principles of microRNA-target recognition. PLoS Biol. 3:e852005. View Article : Google Scholar : PubMed/NCBI
34	Krek A, Grün D, Poy MN, Wolf R, et al: Combinatorial microRNA target predictions. Nat Genet. 37:495–500. 2005. View Article : Google Scholar : PubMed/NCBI
35	Zhao W, Huang CC, Otterson GA, Leon ME, Tang Y, Shilo K and Villalona MA: Altered p16(INK4) and RB1 expressions are associated with poor prognosis in patients with nonsmall cell lung cancer. J Oncol. 2012:9574372012. View Article : Google Scholar : PubMed/NCBI
36	Wu GQ, Liu NN, Xue XL, Cai LT, Zhang C, Qu QR and Yan XJ: Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy. Asian Pac J Cancer Prev. 15:4153–4158. 2014. View Article : Google Scholar : PubMed/NCBI
37	Ishiguro F, Murakami H, Mizuno T, et al: Membranous expression of activated leukocyte cell adhesion molecule contributes to poor prognosis and malignant phenotypes of non-small-cell lung cancer. J Surg Res. 179:24–32. 2013. View Article : Google Scholar : PubMed/NCBI
38	Tachezy M, Zander H, WoltersEisfeld G, et al: Activated leukocyte cell adhesion molecule (CD166): An ‘inert’ cancer stem cell marker for non-small cell lung cancer? Stem Cells. 32:1429–1436. 2014. View Article : Google Scholar : PubMed/NCBI