miR‑671‑5p inhibits gastric cancer cell proliferation and promotes cell apoptosis by targeting URGCP

Qiu,Tiefeng; Wang,Keping; Li,Xianwen; Jin,Jianhua

doi:10.3892/etm.2018.6813

miR‑671‑5p inhibits gastric cancer cell proliferation and promotes cell apoptosis by targeting URGCP

Authors:
- Tiefeng Qiu
- Keping Wang
- Xianwen Li
- Jianhua Jin
View Affiliations

Affiliations: Department of Respiratory Medicine, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu 213002, P.R. China, Department of Thoracic Surgery, Chest Hospital of Nanjing, Nanjing, Jiangsu 210029, P.R. China, Department of Medical Oncology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu 213002, P.R. China
Published online on: October 1, 2018 https://doi.org/10.3892/etm.2018.6813
Pages: 4753-4758

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

Various studies have demonstrated that microRNA (miRNA) serves an important role in the development of gastric cancer. However, the expression level, clinical significance and the biological function of miRNA in gastric cancer remain largely unknown. The present study investigated the exact roles of miR‑671‑5p in gastric cancer, confirmed its target and explored its mechanism. Initially, the low expression levels of miR‑671‑5p in gastric cancer cells were confirmed by reverse transcription‑quantitative polymerase chain reaction. TargetScan and MiRanda databases were utilized to forecast the target genes of miR‑671‑5p, and the prediction was verified by dual‑luciferase reporter assay and western blot analysis. Cell Counting Kit‑8 was used for cell proliferation detection. An annexin V‑fluorescein isothiocyanate kit was used for cell apoptosis determination. Western blot analysis was adopted to measure the protein expression levels in different groups. The results of the present study revealed that there were lower expression levels of miR‑671‑5p in gastric cancer cells than in normal gastric cells. Upregulator of cell proliferation (URGCP) is a direct target of miR‑671‑5p and it may be negatively regulated by miR‑671‑5p. miR‑671‑5p mimics induced reduction of MKN28 cell proliferation. miR‑671‑5p mimics caused upregulation of MKN28 cell apoptosis. In addition, western blotting results indicated that the ratio of B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein was significantly decreased in the miR‑671‑5p mimic group compared with the negative control group (P<0.01). These results suggested that miR‑671‑5p had a protective role in gastric cancer through inhibiting gastric cancer cell proliferation and promoting cell apoptosis by targeting URGCP. Therefore, miR‑671‑5p may be an effective therapeutic target for gastric cancer.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, Negri E, La Vecchia C and Lunet N: Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 50:1330–1344. 2014. View Article : Google Scholar : PubMed/NCBI
3	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
4	Guggenheim DE and Shah MA: Gastric cancer epidemiology and risk factors. J Surg Oncol. 107:230–236. 2013. View Article : Google Scholar : PubMed/NCBI
5	Coburn NG: Lymph nodes and gastric cancer. J Surg Oncol. 99:199–206. 2009. View Article : Google Scholar : PubMed/NCBI
6	Shi Y and Zhou Y: The role of surgery in the treatment of gastric cancer. J Surg Oncol. 101:687–692. 2010. View Article : Google Scholar : PubMed/NCBI
7	Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, et al: Treatment of gastric cancer. World J Gastroenterol. 20:1635–1649. 2014. View Article : Google Scholar : PubMed/NCBI
8	Kelley JR and Duggan JM: Gastric cancer epidemiology and risk factors. J Clin Epidemiol. 56:1–9. 2003. View Article : Google Scholar : PubMed/NCBI
9	Hu Q, Sun W, Wang C and Gu Z: Recent advances of cocktail chemotherapy by combination drug delivery systems. Adv Drug Deliv Rev. 98:19–34. 2016. View Article : Google Scholar : PubMed/NCBI
10	Zhang H: Apatinib for molecular targeted therapy in tumor. Drug Des Devel Ther. 9:6075–6081. 2015. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
12	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
13	Mendell JT: MicroRNAs: Critical regulators of development, cellular physiology and malignancy. Cell Cycle. 4:1179–1184. 2005. View Article : Google Scholar : PubMed/NCBI
14	Jansson MD and Lund AH: MicroRNA and cancer. Mol Oncol. 6:590–610. 2012. View Article : Google Scholar : PubMed/NCBI
15	Chang S, He S, Qiu G, Lu J, Wang J, Liu J, Fan L, Zhao W and Che X: MicroRNA-125b promotes invasion and metastasis of gastric cancer by targeting STARD13 and NEU1. Tumour Biol. 37:12141–12151. 2016. View Article : Google Scholar : PubMed/NCBI
16	Yu B, Lv X, Su L, Li J, Yu Y, Gu Q, Yan M, Zhu Z and Liu B: MiR-148a functions as a tumor suppressor by targeting CCK-BR via inactivating STAT3 and Akt in human gastric cancer. PLoS One. 11:e01589612016. View Article : Google Scholar : PubMed/NCBI
17	Yin G, Zhou H, Xue Y, Yao B and Zhao W: MicroRNA-340 promotes the tumor growth of human gastric cancer by inhibiting cyclin G2. Oncol Rep. 36:1111–1118. 2016. View Article : Google Scholar : PubMed/NCBI
18	Cai J, Li R, Xu X, Zhang L, Wu S, Yang T, Fang L, Wu J, Zhu X, Li M and Huang Y: URGCP promotes non-small cell lung cancer invasiveness by activating the NF-κB-MMP-9 pathway. Oncotarget. 6:36489–36504. 2015. View Article : Google Scholar : PubMed/NCBI
19	Papp G, Krausz T, Stricker TP, Szendrői M and Sápi Z: SMARCB1 expression in epithelioid sarcoma is regulated by miR-206, miR-381, and miR-671-5p on both mRNA and protein levels. Genes Chromosomes Cancer. 53:168–176. 2014. View Article : Google Scholar : PubMed/NCBI
20	Xie C, Song LB, Wu JH, Li J, Yun JP, Lai JM, Xie DY, Lin BL, Yuan YF, Li M and Gao ZL: Upregulator of cell proliferation predicts poor prognosis in hepatocellular carcinoma and contributes to hepatocarcinogenesis by downregulating FOXO3a. PLoS One. 7:e406072012. View Article : Google Scholar : PubMed/NCBI
21	Li WP and Zhou N: URG4 upregulation is associated with tumor growth and poor survival in epithelial ovarian cancer. Arch Gynecol Obstet. 286:209–215. 2012. View Article : Google Scholar : PubMed/NCBI
22	Huang J, Zhu B, Lu L, Lian Z, Wang Y, Yang X, Satiroglu-Tufan NL, Liu J and Luo Z: The expression of novel gene URG4 in osteosarcoma: Correlation with patients' prognosis. Pathology. 41:149–154. 2009. View Article : Google Scholar : PubMed/NCBI
23	Bossel Ben-Moshe N, Avraham R, Kedmi M, Zeisel A, Yitzhaky A, Yarden Y and Domany E: Context-specific microRNA analysis: Identification of functional microRNAs and their mRNA targets. Nucleic Acids Res. 40:10614–10627. 2012. View Article : Google Scholar : PubMed/NCBI
24	Zhang X, Peng Y, Jin Z, Huang W, Cheng Y, Liu Y, Feng X, Yang M, Huang Y, Zhao Z, et al: Integrated miRNA profiling and bioinformatics analyses reveal potential causative miRNAs in gastric adenocarcinoma. Oncotarget. 6:32878–32889. 2015. View Article : Google Scholar : PubMed/NCBI
25	Song J, Xie H, Lian Z, Yang G, Du R, Du Y, Zou X, Jin H, Gao J, Liu J and Fan D: Enhanced cell survival of gastric cancer cells by a novel gene URG4. Neoplasia. 8:995–1002. 2006. View Article : Google Scholar : PubMed/NCBI
26	Marano L, Boccardi V, Braccio B, Esposito G, Grassia M, Petrillo M, Pezzella M, Porfidia R, Reda G, Romano A, et al: Comparison of the 6th and 7th editions of the AJCC/UICC TNM staging system for gastric cancer focusing on the ‘N’ parameter-related survival: The monoinstitutional NodUs Italian study. World J Surg Oncol. 13:2152015. View Article : Google Scholar : PubMed/NCBI
27	Capes-Davis A, Theodosopoulos G, Atkin I, Drexler HG, Kohara A, MacLeod RA, Masters JR, Nakamura Y, Reid YA, Reddel RR and Freshney RI: Check your cultures A list of cross-contaminated or misidentified cell lines. Int J Cancer. 127:1–8. 2010. View Article : Google Scholar : PubMed/NCBI
28	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
29	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
30	Petrocca F, Pilozzi E, Rapazzotti M, Aurello P, Mercantini P, Volinia S, Ruco L, Croce CM and Vecchione A: MicroRNAs deregulation in gastric cancer. Cancer Res. 66:13382006.
31	Barbagallo D, Condorelli A, Ragusa M, Salito L, Sammito M, Banelli B, Caltabiano R, Barbagallo G, Zappalà A, Battaglia R, et al: Dysregulated miR-671-5p/CDR1-AS/CDR1/VSNL1 axis is involved in glioblastoma multiforme. Oncotarget. 7:4746–4759. 2016. View Article : Google Scholar : PubMed/NCBI
32	Tan X, Fu Y, Chen L, Lee W, Lai Y, Rezaei K, Tabbara S, Latham P, Teal CB, Man YG, et al: miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer. Oncotarget. 7:293–307. 2016.PubMed/NCBI
33	Song J, Xie H, Lian Z, Yang G, Du R, Du Y, Zou X, Jin H, Gao J, Liu J and Fan D: Enhanced cell survival of gastric cancer cells by a novel gene URG4. Neoplasia. 8:995–1002. 2006. View Article : Google Scholar : PubMed/NCBI