MicroRNA-454 inhibits the malignant biological behaviours of gastric cancer cells by directly targeting mitogen-activated protein kinase 1 Retraction in /10.3892/or.2022.8276

Wang,Xiaodong; Liu,Baichun; Wen,Fuxing; Song,Ying

doi:10.3892/or.2017.6171

MicroRNA-454 inhibits the malignant biological behaviours of gastric cancer cells by directly targeting mitogen-activated protein kinase 1

Retraction in: /10.3892/or.2022.8276

Authors:
- Xiaodong Wang
- Baichun Liu
- Fuxing Wen
- Ying Song
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Affiliations: Department of Digestive Endoscopy, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of General Medicine, The General Hospital of China National Petroleum Corporation in Jilin, Jilin 132021, P.R. China
Published online on: December 20, 2017 https://doi.org/10.3892/or.2017.6171
Pages: 1494-1504

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Abstract

Gastric cancer (GC) is the fifth most commonly diagnosed malignant disease and the third leading cause of cancer‑related deaths worldwide. Recently, numerous microRNAs (miRNAs) have been determined to contribute to GC initiation and progression, suggesting that miRNAs may be developed as effective diagnostic and prognostic molecular biomarkers and can be investigated as therapeutic targets for patients with this disease. Therefore, further investigation of the miRNAs involved in GC development represents an opportunity to improve the prognosis of GC patients. miRNA‑454 (miR‑454) is abnormally expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanism of miR‑454 in GC remain unclear and require further investigation. In the present study, we assessed miR‑454 expression in GC tissues and cell lines. We also explored the effects of miR‑454 on the biological behaviours of tumour cells and the underlying molecular mechanisms of miR‑454. The results revealed that miR‑454 was significantly downregulated in GC tissues and cell lines. Low miR‑454 expression was positively associated with lymph node metastasis, invasive depth and TNM stage. Additionally, upregulation of miR‑454 inhibited cell proliferation and invasion and induced the apoptosis of the GC cells. Subsequently, mitogen‑activated protein kinase 1 (MAPK1) was identified as a direct target of miR‑454. MAPK1 was upregulated in GC tissues and was found to be negatively correlated with the miR‑454 expression level. Downregulation of MAPK1 also suppressed GC cell proliferation and invasion and increased apoptosis, thereby resembling the suppressive effects of miR‑454 overexpression in GC. Moreover, upregulation of MAPK1 reversed the tumour‑suppressive effects of miR‑454 in GC. Collectively, our data demonstrated that miR‑454 may play tumour‑suppressing roles in GC through the regulation of MAPK1, suggesting that miR‑454 may be a novel biomarker and therapeutic target for patients with this disease.

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1	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
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Chiba T: Factors contributing to the development of gastric cancer due to Helicobacter pylori infection. Curr Gastroenterol Rep. 4:267–268. 2002. View Article : Google Scholar : PubMed/NCBI
4	Cancer Genome Atlas Research Network, . Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513:202–209. 2014. View Article : Google Scholar : PubMed/NCBI
5	Lent MR, Hayes SM, Wood GC, Napolitano MA, Argyropoulos G, Gerhard GS, Foster GD and Still CD: Smoking and alcohol use in gastric bypass patients. Eat Behav. 14:460–463. 2013. View Article : Google Scholar : PubMed/NCBI
6	Kanda M, Kodera Y and Sakamoto J: Updated evidence on adjuvant treatments for gastric cancer. Expert Rev Gastroenterol Hepatol. 9:1549–1560. 2015. View Article : Google Scholar : PubMed/NCBI
7	Moon YW, Jeung HC, Rha SY, Yoo NC, Roh JK, Noh SH, Kim BS and Chung HC: Changing patterns of prognosticators during 15-year follow-up of advanced gastric cancer after radical gastrectomy and adjuvant chemotherapy: A 15-year follow-up study at a single korean institute. Ann Surg Oncol. 14:2730–2737. 2007. View Article : Google Scholar : PubMed/NCBI
8	Chaffer CL and Weinberg RA: A perspective on cancer cell metastasis. Science. 331:1559–1564. 2011. View Article : Google Scholar : PubMed/NCBI
9	Xu W, Yang Z and Lu N: Molecular targeted therapy for the treatment of gastric cancer. J Exp Clin Cancer Res. 35:12016. View Article : Google Scholar : PubMed/NCBI
10	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
11	He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI
12	Zheng N, Yang P, Wang Z and Zhou Q: OncomicroRNAs-mediated tumorigenesis: Implication in cancer diagnosis and targeted therapy. Curr Cancer Drug Targets. 17:40–47. 2017. View Article : Google Scholar : PubMed/NCBI
13	Jiang C, Chen X, Alattar M, Wei J and Liu H: MicroRNAs in tumorigenesis, metastasis, diagnosis and prognosis of gastric cancer. Cancer Gene Ther. 22:291–301. 2015. View Article : Google Scholar : PubMed/NCBI
14	Ding L, Zhang S, Xu M, Zhang R, Sui P and Yang Q: MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2. J Exp Clin Cancer Res. 36:452017. View Article : Google Scholar : PubMed/NCBI
15	Wu D, Niu X, Pan H, Zhou Y, Qu P and Zhou J: MicroRNA-335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1. Mol Med Rep. 13:4379–4385. 2016. View Article : Google Scholar : PubMed/NCBI
16	Li Y, Sun Z, Liu B, Shan Y, Zhao L and Jia L: Tumor-suppressive miR-26a and miR-26b inhibit cell aggressiveness by regulating FUT4 in colorectal cancer. Cell Death Dis. 8:e28922017. View Article : Google Scholar : PubMed/NCBI
17	Lv QL, Du H, Liu YL, Huang YT, Wang GH, Zhang X, Chen SH and Zhou HH: Low expression of microRNA-320b correlates with tumorigenesis and unfavorable prognosis in glioma. Oncol Rep. 38:959–966. 2017. View Article : Google Scholar : PubMed/NCBI
18	Qiu J, Hao Y, Huang S, Ma Y, Li X, Li D and Mao Y: miR-557 works as a tumor suppressor in human lung cancers by negatively regulating LEF1 expression. Tumour Biol. 39:10104283177094672017. View Article : Google Scholar : PubMed/NCBI
19	Pan HW, Li SC and Tsai KW: MicroRNA dysregulation in gastric cancer. Curr Pharm Des. 19:1273–1284. 2013. View Article : Google Scholar : PubMed/NCBI
20	Wu WK, Lee CW, Cho CH, Fan D, Wu K, Yu J and Sung JJ: MicroRNA dysregulation in gastric cancer: A new player enters the game. Oncogene. 29:5761–5771. 2010. View Article : Google Scholar : PubMed/NCBI
21	Wang H, Jiang Z, Chen H, Wu X, Xiang J and Peng J: MicroRNA-495 inhibits gastric cancer cell migration and invasion possibly via targeting high mobility group AT-Hook 2 (HMGA2). Med Sci Monit. 23:640–648. 2017. View Article : Google Scholar : PubMed/NCBI
22	Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI
23	Sun L, Wang Q, Gao X, Shi D, Mi S and Han Q: MicroRNA-454 functions as an oncogene by regulating PTEN in uveal melanoma. FEBS Lett. 589:2791–2796. 2015. View Article : Google Scholar : PubMed/NCBI
24	Liang HL, Hu AP, Li SL, Xie JP, Ma QZ and Liu JY: miR-454 prompts cell proliferation of human colorectal cancer cells by repressing CYLD expression. Asian Pac J Cancer Prev. 16:2397–2402. 2015. View Article : Google Scholar : PubMed/NCBI
25	Fang B, Zhu J, Wang Y, Geng F and Li G: miR-454 inhibited cell proliferation of human glioblastoma cells by suppressing PDK1 expression. Biomed Pharmacother. 75:148–152. 2015. View Article : Google Scholar : PubMed/NCBI
26	Niu G, Li B, Sun J and Sun L: miR-454 is down-regulated in osteosarcomas and suppresses cell proliferation and invasion by directly targeting c-Met. Cell Prolif. 48:348–355. 2015. View Article : Google Scholar : PubMed/NCBI
27	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
28	Liang B, Wang S, Zhu XG, Yu YX, Cui ZR and Yu YZ: Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer. World J Gastroenterol. 11:623–628. 2005. View Article : Google Scholar : PubMed/NCBI
29	Husain SS, Szabo IL, Pai R, Soreghan B, Jones MK and Tarnawski AS: MAPK (ERK2) kinase-a key target for NSAIDs-induced inhibition of gastric cancer cell proliferation and growth. Life Sci. 69:3045–3054. 2001. View Article : Google Scholar : PubMed/NCBI
30	Zhao Y, Zhao X, Yang B, Neuzil J and Wu K: alpha-Tocopheryl succinate-induced apoptosis in human gastric cancer cells is modulated by ERK1/2 and c-Jun N-terminal kinase in a biphasic manner. Cancer Lett. 247:345–352. 2007. View Article : Google Scholar : PubMed/NCBI
31	Mao J, Xu Z, Fang Y, Wang H, Xu J, Ye J, Zheng S and Zhu Y: Hepatoma-derived growth factor involved in the carcinogenesis of gastric epithelial cells through promotion of cell proliferation by Erk1/2 activation. Cancer Sci. 99:2120–2127. 2008. View Article : Google Scholar : PubMed/NCBI
32	Cao Y, Tu Y, Mei J, Li Z, Jie Z, Xu S, Xu L, Wang S and Xiong Y: RNAimediated knockdown of PRL-3 inhibits cell invasion and downregulates ERK 1/2 expression in the human gastric cancer cell line, SGC-7901. Mol Med Rep. 7:1805–1811. 2013. View Article : Google Scholar : PubMed/NCBI
33	Fei B and Wu H: miR-378 inhibits progression of human gastric cancer MGC-803 cells by targeting MAPK1 in vitro. Oncol Res. 20:557–564. 2012. View Article : Google Scholar : PubMed/NCBI
34	Shrestha S, Hsu SD, Huang WY, Huang HY, Chen W, Weng SL and Huang HD: A systematic review of microRNA expression profiling studies in human gastric cancer. Cancer Med. 3:878–888. 2014. View Article : Google Scholar : PubMed/NCBI
35	Zhu X, Lv M, Wang H and Guan W: Identification of circulating microRNAs as novel potential biomarkers for gastric cancer detection: A systematic review and meta-analysis. Dig Dis Sci. 59:911–919. 2014. View Article : Google Scholar : PubMed/NCBI
36	Rao M, Zhu Y, Zhou Y, Cong X and Feng L: MicroRNA-122 inhibits proliferation and invasion in gastric cancer by targeting CREB1. Am J Cancer Res. 7:323–333. 2017.PubMed/NCBI
37	Cheng J, Chen Y, Zhao P, Li N, Lu J, Li J, Liu Z, Lv Y and Huang C: Dysregulation of miR-638 in hepatocellular carcinoma and its clinical significance. Oncol Lett. 13:3859–3865. 2017. View Article : Google Scholar : PubMed/NCBI
38	Maia D, de Carvalho AC, Horst MA, Carvalho AL, Scapulatempo-Neto C and Vettore AL: Expression of miR-296-5p as predictive marker for radiotherapy resistance in early-stage laryngeal carcinoma. J Transl Med. 13:2622015. View Article : Google Scholar : PubMed/NCBI
39	Cao ZG, Li JJ, Yao L, Huang YN, Liu YR, Hu X, Song CG and Shao ZM: High expression of microRNA-454 is associated with poor prognosis in triple-negative breast cancer. Oncotarget. 7:64900–64909. 2016. View Article : Google Scholar : PubMed/NCBI
40	Zhu DY, Li XN, Qi Y, Liu DL, Yang Y, Zhao J, Zhang CY, Wu K and Zhao S: miR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN. Biomed Pharmacother. 81:79–85. 2016. View Article : Google Scholar : PubMed/NCBI
41	Zhou L, Qu YM, Zhao XM and Yue ZD: Involvement of miR-454 overexpression in the poor prognosis of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 20:825–829. 2016.PubMed/NCBI
42	Fan Y, Shi C, Li T and Kuang T: microRNA-454 shows anti-angiogenic and anti-metastatic activity in pancreatic ductal adenocarcinoma by targeting LRP6. Am J Cancer Res. 7:139–147. 2017.PubMed/NCBI
43	Fan Y, Xu LL, Shi CY, Wei W, Wang DS and Cai DF: MicroRNA-454 regulates stromal cell derived factor-1 in the control of the growth of pancreatic ductal adenocarcinoma. Sci Rep. 6:227932016. View Article : Google Scholar : PubMed/NCBI
44	Yu L, Gong X, Sun L, Yao H, Lu B and Zhu L: miR-454 functions as an oncogene by inhibiting CHD5 in hepatocellular carcinoma. Oncotarget. 6:39225–39234. 2015. View Article : Google Scholar : PubMed/NCBI
45	Wei C, Luo Q, Sun X, Li D, Song H, Li X, Song J, Hua K and Fang L: MicroRNA-497 induces cell apoptosis by negatively regulating Bcl-2 protein expression at the posttranscriptional level in human breast cancer. Int J Clin Exp Pathol. 8:7729–7739. 2015.PubMed/NCBI
46	Seger R and Krebs EG: The MAPK signaling cascade. FASEB J. 9:726–735. 1995. View Article : Google Scholar : PubMed/NCBI
47	Li W, Liang J, Zhang Z, Lou H, Zhao L, Xu Y and Ou R: MicroRNA-329-3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer. Oncol Rep. 37:2743–2750. 2017. View Article : Google Scholar : PubMed/NCBI
48	Yiwei T, Hua H, Hui G, Mao M and Xiang L: HOTAIR Interacting with MAPK1 regulates ovarian cancer skov3 cell proliferation, migration, and invasion. Med Sci Monit. 21:1856–1863. 2015. View Article : Google Scholar : PubMed/NCBI
49	You B, Yang YL, Xu Z, Dai Y, Liu S, Mao JH, Tetsu O, Li H, Jablons DM and You L: Inhibition of ERK1/2 down-regulates the Hippo/YAP signaling pathway in human NSCLC cells. Oncotarget. 6:4357–4368. 2015. View Article : Google Scholar : PubMed/NCBI
50	Kouhkan F, Mobarra N, Soufi-Zomorrod M, Keramati F, Hosseini Rad SM, Fathi-Roudsari M, Tavakoli R, Hajarizadeh A, Ziaei S, Lahmi R, et al: MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1. J Med Genet. 53:24–33. 2016. View Article : Google Scholar : PubMed/NCBI
51	Tsubaki M, Takeda T, Ogawa N, Sakamoto K, Shimaoka H, Fujita A, Itoh T, Imano M, Ishizaka T, Satou T and Nishida S: Overexpression of survivin via activation of ERK1/2, Akt, and NF-κB plays a central role in vincristine resistance in multiple myeloma cells. Leuk Res. 39:445–452. 2015. View Article : Google Scholar : PubMed/NCBI