MicroRNA‑150‑5p and SRC kinase signaling inhibitor 1 involvement in the pathological development of gastric cancer

Quan,Xiyun; Chen,Dongliang; Li,Ming; Chen,Xun; Huang,Meiyuan

doi:10.3892/etm.2019.7828

MicroRNA‑150‑5p and SRC kinase signaling inhibitor 1 involvement in the pathological development of gastric cancer

Authors:
- Xiyun Quan
- Dongliang Chen
- Ming Li
- Xun Chen
- Meiyuan Huang
View Affiliations

Affiliations: Department of Pathology, Zhuzhou Central Hospital, Zhuzhou, Hunan 412000, P.R. China, Department of Emergency, Zhuzhou Central Hospital, Zhuzhou, Hunan 412000, P.R. China, Department of Hepatic Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan 412000, P.R. China
Published online on: July 30, 2019 https://doi.org/10.3892/etm.2019.7828
Pages: 2667-2674

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

The current study aimed to assess the regulatory mechanism of microRNA‑150‑5p (miR‑150‑5p) in the pathogenesis of gastric cancer. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to verify the expression of miR‑150‑5p in gastric cancer tissues and cell lines, which was revealed to be highly expressed in each. In addition, the expression of miR‑150‑5p was associated with advanced gastric cancer and lymph node metastasis. The current study then hypothesized that SRC kinase signaling inhibitor 1 (SRCIN1) was the target gene of miR‑150‑5p, a theory that was confirmed via a dual luciferase reporter gene assay. RT‑qPCR and western blotting were then performed to verify the expression of SRCIN1 in gastric cancer tissues and cell lines. The results demonstrated that SRCIN1 was lowly expressed in gastric cancer tissues and cells. To assess the effect of miR‑150‑5p on gastric cancer cells, experiments were conducted with BGC‑823 cells transfected with a miR‑150‑5p inhibitor or a miR‑150‑5p inhibitor+SRCIN1‑small interfering (si)RNA respectively. A cell counting kit‑8 assay and flow cytometry were also used to assess cell viability and apoptosis, respectively. Western blotting and RT‑qPCR were further used to measure the expression of specific markers of epithelial mesenchymal transition (EMT), including epithelial cell markers (E‑cadherin and zona occluding‑1) and interstitial cell markers (vimentin, N‑cadherin and β‑catenin). The results revealed that the miR‑150‑5p inhibitor attenuated cell viability, induced apoptosis, decreased the expression of interstitial cell markers and increased epithelial cell marker expression. However, all effects of the miR‑150‑5p inhibitor were reversed following SRCIN1‑siRNA treatment. In summary, the current study indicated that the miR‑150‑5p inhibitor attenuated cell viability, induced apoptosis and inhibited gastric cancer cell EMT by targeting SRCIN1.

View Figures

View References

1	Yu ZY, Wang Z, Lee KY, Yuan P and Ding J: Effect of silencing colon cancer-associated transcript 2 on the proliferation, apoptosis and autophagy of gastric cancer BGC-823 cells. Oncol Lett. 15:3127–3132. 2018.PubMed/NCBI
2	Salem M, Xiu J, Eldeiry W, Reddy S, Philip P, Gatalica Z, Khan S, Denlinger C, Mikhail S, Smaglo B, et al: Comparative molecular analyses of esophageal adenocarcinoma, esophageal squamous cell carcinoma and gastric adenocarcinoma, and impact of molecular profile on outcome. Ann Oncol. 27:ii119. 2016. View Article : Google Scholar
3	Fu L, Yin F, Li XR, Han BK, Zhang C, Wang JW, Wang YQ, Bi YF and Liu HM: Generation and characterization of a paclitaxel-resistant human gastric carcinoma cell line. Anticancer Drugs. 1:491–502. 2018. View Article : Google Scholar
4	Yang BF, Cai W and Chen B: LncRNA SNHG12 regulated the proliferation of gastric carcinoma cell BGC-823 by targeting microRNA-199a/b-5p. Eur Rev Med Pharmacol Sci. 22:1297–1306. 2018.PubMed/NCBI
5	Liu L, Si N, Ma Y, Ge D, Yu X, Fan A, Wang X, Hu J, Wei P, Ma L, et al: Hydroxysafflor-yellow A induces human gastric carcinoma BGC-823 cell apoptosis by activating peroxisome proliferator-activated receptor gamma (PPARγ). Med Sci Monit. 24:803–811. 2018. View Article : Google Scholar : PubMed/NCBI
6	Rothmiller S, Wolf M, Worek F, Steinritz D, Thiermann H and Schmidt A: Alteration of miRNA expression in a sulfur mustard resistant cell line. Toxicol Lett. 293:38–44. 2018. View Article : Google Scholar : PubMed/NCBI
7	Ultimo S, Martelli AM, Zauli G, Vitale M, Calin GA and Neri LM: Roles and clinical implications of MicroRNAs in acute lymphoblastic leukemia. J Cell Physiol. 233:5642–5654. 2018. View Article : Google Scholar : PubMed/NCBI
8	Sheng N, Zhang L and Yang S: MicroRNA-429 decreases the invasion ability of gastric cancer cell line BGC-823 by downregulating the expression of heparanase. Exp Ther Med. 15:1927–1933. 2018.PubMed/NCBI
9	Meng Y, Tian H, Hu Q, Liang H, Zeng L and Xiao H: MicroRNA repertoire and comparative analysis of Andrias davidianus infected with ranavirus using deep sequencing. Dev Comp Immunol. 85:108–114. 2018. View Article : Google Scholar : PubMed/NCBI
10	Yan J, Li X, Peng L, Shen X, Dang Y and Zhang G: MicroRNA-150 as a potential biomarker in diagnosis of cancer: A meta-analysis. Clin Lab. 63:1187–1197. 2017. View Article : Google Scholar : PubMed/NCBI
11	Li C, Du X, Xia S and Chen L: MicroRNA-150 inhibits the proliferation and metastasis potential of colorectal cancer cells by targeting iASPP. Oncol Rep. 40:252–260. 2018.PubMed/NCBI
12	Tang W, Xu P, Wang H, Niu Z, Zhu D, Lin Q, Tang L and Ren L: MicroRNA-150 suppresses triple-negative breast cancer metastasis through targeting HMGA2. Onco Targets Ther. 11:2319–2332. 2018. View Article : Google Scholar : PubMed/NCBI
13	Sun X, Zhang C, Cao Y and Liu E: miR-150 suppresses tumor growth in melanoma through downregulation of MYB. Oncol Res. 27:317–323. 2019. View Article : Google Scholar : PubMed/NCBI
14	Zhang Z, Wang J, Li J, Wang X and Song W: MicroRNA-150 promotes cell proliferation, migration and invasion of cervical cancer through targeting PDCD4. Biomed Pharmacother. 97:511–517. 2018. View Article : Google Scholar : PubMed/NCBI
15	Koshizuka K, Hanazawa T, Kikkawa N, Katada K, Okato A, Arai T, Idichi T, Osako Y, Okamoto Y and Seki N: Antitumor miR-150-5p and miR-150-3p, inhibit cancer cell aggressiveness by targeting SPOCK1, in head and neck squamous cell carcinoma. Auris Nasus Larynx. 45:854–865. 2018. View Article : Google Scholar : PubMed/NCBI
16	Yan R, Yang T, Zhai H, Zhou Z, Gao L and Li Y: MicroRNA-150-5p affects cell proliferation, apoptosis and EMT by regulation of the BRAFV600E mutation in papillary thyroid cancer cells. J Cell Biochem. 119:8763–8772. 2018. View Article : Google Scholar : PubMed/NCBI
17	Ergun S, Güney S, Temiz E, Petrovic N and Gunes S: Significance of Mir-15a-5p and Cnksr3 as novel prognostic biomarkers in non-small cell lung cancer. Anticancer Agents Med Chem. 18:1695–1701. 2018. View Article : Google Scholar : PubMed/NCBI
18	Yu J, Feng Y, Wang Y and An R: Aryl hydrocarbon receptor enhances the expression of miR-150-5p to suppress in prostate cancer progression by regulating MAP3K12. Arch Biochem Biophys. 654:47–54. 2018. View Article : Google Scholar : PubMed/NCBI
19	Suetsugu T, Koshizuka K, Seki N, Mizuno K, Okato A, Arai T, Misono S, Uchida A, Kumamoto T and Inoue H: Downregulation of matrix metalloproteinase 14 by the antitumor miRNA, miR-150-5p, inhibits the aggressiveness of lung squamous cell carcinoma cells. Int J Oncol. 52:913–924. 2018.PubMed/NCBI
20	Wang S, Yan Y, Cheng Z, Hu Y and Liu T: Sotetsuflavone suppresses invasion and metastasis in non-small-cell lung cancer A549 cells by reversing EMT via the TNF-α/NF-κB and PI3K/AKT signaling pathway. Cell Death Discov. 4:262018. View Article : Google Scholar : PubMed/NCBI
21	Zuo L, Zhao H, Yang R, Wang L, Ma H, Xu X, Zhou P and Kong L: Lamin A/C might be involved in the EMT signalling pathway. Gene. 663:51–64. 2018. View Article : Google Scholar : PubMed/NCBI
22	Yang Y, Gao M, Lin Z, Chen L, Jin Y, Zhu G, Wang Y and Jin T: DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer. Oncotarget. 8:98708–98722. 2017.PubMed/NCBI
23	Pal M, Bhattacharya S, Kalyan G and Hazra S: Cadherin profiling for therapeutic interventions in Epithelial Mesenchymal Transition (EMT) and tumorigenesis. Exp Cell Res. 368:137–146. 2018. View Article : Google Scholar : PubMed/NCBI
24	Ma Z, Xin Z, Hu W, Jiang S, Yang Z, Yan X, Li X, Yang Y and Chen F: Forkhead box O proteins: Crucial regulators of cancer EMT. Semin Cancer Biol. 50:21–31. 2018. View Article : Google Scholar : PubMed/NCBI
25	Liu CY, Lin HH, Tang MJ and Wang YK: Vimentin contributes to epithelial-mesenchymal transition cancer cell mechanics by mediating cytoskeletal organization and focal adhesion maturation. Oncotarget. 6:15966–15983. 2015.PubMed/NCBI
26	Shang S, Hua F and Hu ZW: The regulation of β-catenin activity and function in cancer: Therapeutic opportunities. Oncotarget. 8:33972–33989. 2017. View Article : Google Scholar : PubMed/NCBI
27	Zihni C, Mills C, Matter K and Balda MS: Tight junctions: From simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol. 17:564–580. 2016. 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	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
30	Mellis D and Caporali A: MicroRNA-based therapeutics in cardiovascular disease: Screening and delivery to the target. Biochem Soc Trans. 46:11–21. 2018. View Article : Google Scholar : PubMed/NCBI
31	Cao DD, Li L and Chan WY: MicroRNAs: Key regulators in the central nervous system and their implication in neurological diseases. Int J Mol Sci. 17(pii): E8422016. View Article : Google Scholar : PubMed/NCBI
32	Mannucci C, Casciaro M, Minciullo PL, Calapai G, Navarra M and Gangemi S: Involvement of microRNAs in skin disorders: A literature review. Allergy Asthma Proc. 38:9–15. 2017. View Article : Google Scholar : PubMed/NCBI
33	Hu L, Ai J, Long H, Liu W, Wang X, Zuo Y, Li Y, Wu Q and Deng Y: Intergrative microRNA and gene profiling data analysis reveals novel biomarkers and mechanisms for lung cancer. Oncotarget. 7:8441–8454. 2016.PubMed/NCBI
34	Tsai MM, Wang CS, Tsai CY, Huang HW, Chi HC, Lin YH, Lu PH and Lin KH: Potential diagnostic, prognostic and therapeutic targets of microRNAs in human gastric cancer. Int J Mol Sci. 17(pii): E9452016. View Article : Google Scholar : PubMed/NCBI
35	Zhao H, Li M, Li L, Yang X, Lan G and Zhang Y: MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion and promotes apoptosis. PLoS One. 8:e835712013. View Article : Google Scholar : PubMed/NCBI
36	Kaukoniemi KM, Rauhala HE, Scaravilli M, Latonen L, Annala M, Vessella RL, Nykter M, Tammela TL and Visakorpi T: Epigenetically altered miR-193b targets cyclin D1 in prostate cancer. Cancer Med. 4:1417–1425. 2015. View Article : Google Scholar : PubMed/NCBI
37	Schmidt A, Steinritz D, Thiermann H, Meineke V and Abend M: Alteration of miRNA expression in early endothelial cells after exposure with sub-lethal sulfur mustard concentrations. Toxicol Lett. 244:88–94. 2016. View Article : Google Scholar : PubMed/NCBI
38	Gharbi S, Khateri S, Soroush MR, Shamsara M, Naeli P, Najafi A, Korsching E and Mowla SJ: MicroRNA expression in serum samples of sulfur mustard veterans as a diagnostic gateway to improve care. PLoS One. 13:e01945302018. View Article : Google Scholar : PubMed/NCBI
39	Ma M, Zhao J, Wu Q, Xiao K, Li S, Zhu H, Liu C, Xie H and Zuo C: MiRNA-545 negatively regulates the oncogenic activity of EMS1 in gastric cancer. Cancer Med. 7:2452–2462. 2018. View Article : Google Scholar : PubMed/NCBI
40	Liao Y, Liao Y, Li J, Xiao K, Li S, Zhu H, Liu C, Xie H and Zuo C: Genetic variants in miRNA machinery genes associated with clinicopathological characteristics and outcomes of gastric cancer patients. Int J Biol Markers. 33:301–307. 2018. View Article : Google Scholar : PubMed/NCBI