miR-127 suppresses gastric cancer cell migration and invasion via targeting Wnt7a

Wang,Linlin; Wang,Xufei; Jiang,Xuefeng

doi:10.3892/ol.2019.9955

miR-127 suppresses gastric cancer cell migration and invasion via targeting Wnt7a

Authors:
- Linlin Wang
- Xufei Wang
- Xuefeng Jiang
View Affiliations

Affiliations: Ultrasound Department of China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of Opthalmology, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China, Gastroenterology Department of China-Japan Union Hospital, Jilin University, Changchun, Jilin 130000, P.R. China
Published online on: January 21, 2019 https://doi.org/10.3892/ol.2019.9955
Pages: 3219-3226
Copyright: © Wang 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

Gastric cancer (GC) is a malignant tumor originating from the mucosal epithelium of the stomach. Patients suffering from this disease may have occurrence of residual GC due to delay in diagnosis and treatment. In addition, abnormal expression of microRNAs (miRNAs) is involved in GC progression. Therefore, we examined the underlying mechanism of miR-127 in GC. The expression of miR-127 and Wnt7a was examined in GC using RT-qPCR and western blot analysis. A Transwell assay was used to assess the ability of GC cell migration and invasion. Luciferase reporter assay was used to verify the specific target of miR-127 in GC. The results showed miR-127 expression was lower in GC than normal samples, while Wnt7a expression was detected at a higher level in GC than normal samples. The association between miR-127 and Wnt7a expression was negatively correlated in GC tissues. miR-127 mimic in the two GC cell lines markedly curbed cell migration and invasion, while inhibition of miR-127 showed the opposite effect. In addition, Wnt7a siRNA significantly inhibited GC cell migration and invasion and Wnt7a was verified as a specific target of miR-127 in GC cells. Wnt7a reversed the ability of GC cell migration and invasion regulated by miR-127. In conclusion, miR-127 could curb GC cell migration and invasion by upregulating Wnt7a, indicating its potential application in GC diagnosis and therapy.

View Figures

View References

1	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
2	Chen W, Zheng R, Zhang S, Zhao P, Zeng H, Zou X and He J: Annual report on status of cancer in China, 2010. Chin J Cancer Res. 26:48–58. 2014.PubMed/NCBI
3	Zhang J, Song Y, Zhang C, Zhi X, Fu H, Ma Y, Chen Y, Pan F, Wang K, Ni J, et al: Circulating miR-16-5p and miR-19b-3p as two novel potential biomarkers to indicate progression of gastric cancer. Theranostics. 5:733–745. 2015. View Article : Google Scholar : PubMed/NCBI
4	Di Leva G, Garofalo M and Croce CM: MicroRNAs in cancer. Annu Rev Pathol. 9:287–314. 2014. View Article : Google Scholar : PubMed/NCBI
5	Kohlhapp FJ, Mitra AK, Lengyel E and Peter ME: MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment. Oncogene. 34:5857–5868. 2015. View Article : Google Scholar : PubMed/NCBI
6	Lan H, Lu H, Wang X and Jin H: MicroRNAs as potential biomarkers in cancer: Opportunities and challenges. BioMed Res Int. 2015:1250942015. View Article : Google Scholar : PubMed/NCBI
7	Ge X, Cui H, Zhou Y, Yin D, Feng Y, Xin Q, Xu X, Liu W, Liu S and Zhang Q: miR-320a modulates cell growth and chemosensitivity via regulating ADAM10 in gastric cancer. Mol Med Rep. 16:9664–9670. 2017. View Article : Google Scholar : PubMed/NCBI
8	Ji FJ, Wu YY, An Z, Liu XS, Jiang JN, Chen FF and Fang XD: Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis. Sci Rep. 7:154882017. View Article : Google Scholar : PubMed/NCBI
9	Yang L, Zhang W, Wang Y, Zou T, Zhang B, Xu Y, Pang T, Hu Q, Chen M, Wang L, et al: Hypoxia-induced miR-214 expression promotes tumour cell proliferation and migration by enhancing the Warburg effect in gastric carcinoma cells. Cancer Lett. 414:44–56. 2018. View Article : Google Scholar : PubMed/NCBI
10	Sun GL, Li Z, Wang WZ, Chen Z, Zhang L, Li Q, Wei S, Li BW, Xu JH, Chen L, et al: miR-324-3p promotes gastric cancer development by activating Smad4-mediated Wnt/beta-catenin signaling pathway. J Gastroenterol. Nov 4–2017.(Epub ahead of print). doi: 10.1007/s00535-017-1408-0.
11	Bi L, Yang Q, Yuan J, Miao Q, Duan L, Li F and Wang S: MicroRNA-127-3p acts as a tumor suppressor in epithelial ovarian cancer by regulating the BAG5 gene. Oncol Rep. 36:2563–2570. 2016. View Article : Google Scholar : PubMed/NCBI
12	Yu Y, Liu L, Ma R, Gong H, Xu P and Wang C: MicroRNA-127 is aberrantly downregulated and acted as a functional tumor suppressor in human pancreatic cancer. Tumour Biol. 37:14249–14257. 2016. View Article : Google Scholar : PubMed/NCBI
13	Zhang J, Hou W, Chai M, Zhao H, Jia J, Sun X, Zhao B and Wang R: MicroRNA-127-3p inhibits proliferation and invasion by targeting SETD8 in human osteosarcoma cells. Biochem Biophys Res Commun. 469:1006–1011. 2016. View Article : Google Scholar : PubMed/NCBI
14	Jiang H, Hua D, Zhang J, Lan Q, Huang Q, Yoon JG, Han X, Li L, Foltz G, Zheng S, et al: MicroRNA-127-3p promotes glioblastoma cell migration and invasion by targeting the tumor-suppressor gene SEPT7. Oncol Rep. 31:2261–2269. 2014. View Article : Google Scholar : PubMed/NCBI
15	Doerks T, Copley RR, Schultz J, Ponting CP and Bork P: Systematic identification of novel protein domain families associated with nuclear functions. Genome Res. 12:47–56. 2002. View Article : Google Scholar : PubMed/NCBI
16	Cleary AS, Leonard TL, Gestl SA and Gunther EJ: Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers. Nature. 508:113–117. 2014. View Article : Google Scholar : PubMed/NCBI
17	Tian J, He H and Lei G: Wnt/β-catenin pathway in bone cancers. Tumour Biol. 35:9439–9445. 2014. View Article : Google Scholar : PubMed/NCBI
18	Bikkavilli RK, Avasarala S, Van Scoyk M, Arcaroli J, Brzezinski C, Zhang W, Edwards MG, Rathinam MK, Zhou T, Tauler J, et al: Wnt7a is a novel inducer of β-catenin-independent tumor-suppressive cellular senescence in lung cancer. Oncogene. 34:54062015. View Article : Google Scholar : PubMed/NCBI
19	Hirata T, Zheng Q, Chen Z, Kinoshita H, Okamoto J, Kratz J, Li H, Lui N, Do H, Cheng T, et al: Wnt7A is a putative prognostic and chemosensitivity marker in human malignant pleural mesothelioma. Oncol Rep. 33:2052–2060. 2015. View Article : Google Scholar : PubMed/NCBI
20	Kirikoshi H and Katoh M: Expression of WNT7A in human normal tissues and cancer, and regulation of WNT7A and WNT7B in human cancer. Int J Oncol. 21:895–900. 2002.PubMed/NCBI
21	MacLean JA II, King ML, Okuda H and Hayashi K: WNT7A Regulation by miR-15b in ovarian cancer. PLoS One. 11:e01561092016. View Article : Google Scholar : PubMed/NCBI
22	Ramos-Solano M, Meza-Canales ID, Torres-Reyes LA, Alvarez-Zavala M, Alvarado-Ruíz L, Rincon-Orozco B, Garcia-Chagollan M, Ochoa-Hernández AB, Ortiz-Lazareno PC, Rösl F, et al: Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration. Exp Cell Res. 335:39–50. 2015. View Article : Google Scholar : PubMed/NCBI
23	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
24	Lu M, Ju S, Shen X, Wang X, Jing R, Yang C, Chu H and Cong H: Combined detection of plasma miR-127-3p and HE4 improves the diagnostic efficacy of breast cancer. Cancer Biomark. 18:143–148. 2017. View Article : Google Scholar : PubMed/NCBI
25	Shi L, Wang Y, Lu Z, Zhang H, Zhuang N, Wang B, Song Z, Chen G, Huang C, Xu D, et al: miR-127 promotes EMT and stem-like traits in lung cancer through a feed-forward regulatory loop. Oncogene. 36:1631–1643. 2017. View Article : Google Scholar : PubMed/NCBI
26	Gao X, Wang X, Cai K, Wang W, Ju Q, Yang X, Wang H and Wu H: MicroRNA-127 is a tumor suppressor in human esophageal squamous cell carcinoma through the regulation of oncogene FMNL3. Eur J Pharmacol. 791:603–610. 2016. View Article : Google Scholar : PubMed/NCBI
27	Tsai KW, Wu CW, Hu LY, Li SC, Liao YL, Lai CH, Kao HW, Fang WL, Huang KH, Chan WC, et al: Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer. Int J Cancer. 129:2600–2610. 2011. View Article : Google Scholar : PubMed/NCBI
28	Guo LH, Li H, Wang F, Yu J and He JS: The tumor suppressor roles of miR-433 and miR-127 in gastric cancer. Int J Mol Sci. 14:14171–14184. 2013. View Article : Google Scholar : PubMed/NCBI
29	Polakis P: Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 4:42012. View Article : Google Scholar
30	Katoh Y and Katoh M: Identification and characterization of rat Wnt6 and Wnt10a genes in silico. Int J Mol Med. 15:527–531. 2005.PubMed/NCBI
31	Kim BK, Kim I and Yoon SK: Identification of miR-199a-5p target genes in the skin keratinocyte and their expression in cutaneous squamous cell carcinoma. J Dermatol Sci. 79:137–147. 2015. View Article : Google Scholar : PubMed/NCBI