Direct targeting of MAPK8IP1 by miR-10a-5p is a major mechanism for gastric cancer metastasis

Lu,Yaoyong; Wei,Ganbao; Liu,Liangbo; Mo,Yichao; Chen,Qingsheng; Xu,Lufei; Liao,Rongwei; Zeng,Dehao; Zhang,Kunqiang

doi:10.3892/ol.2016.5544

Direct targeting of MAPK8IP1 by miR-10a-5p is a major mechanism for gastric cancer metastasis

Authors:
- Yaoyong Lu
- Ganbao Wei
- Liangbo Liu
- Yichao Mo
- Qingsheng Chen
- Lufei Xu
- Rongwei Liao
- Dehao Zeng
- Kunqiang Zhang
View Affiliations

Affiliations: Department of Radiation Oncology, Gaozhou People's Hospital, Gaozhou, Guangdong 525200, P.R. China
Published online on: December 28, 2016 https://doi.org/10.3892/ol.2016.5544
Pages: 1131-1136
Copyright: © Lu 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 (miRNA) are endogenous non‑coding RNAs that suppress gene expression at the transcriptional, post-transcriptional or translational level by targeting the 3'-UTRs of specific mRNAs. miR-10a has been frequently reported to be aberrantly overexpressed in human tumors. In gastric cancer (GC), miR‑10a has an important role in the metastasis from primary GC to lymph nodes. However, the role and relevant pathways of miR‑10a in GC metastasis remain largely unknown. The present study was performed using 41 GC and 20 normal gastric mucosa tissues. Reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) analysis demonstrated that MAPK8IP1 was significant downregulated in GC tissue. A statistically significant inverse correlation was detected between miR‑10a and MAPK8IP1 mRNA expression levels in GC specimens. Luciferase reporter assay and qPCR results suggested that MAPK8IP1 was a direct target of miR‑10a in GC cells. Matrigel invasion assay and wound‑healing assay results showed that MAPK8IP1 overexpression rescued the increased migration ability of miR‑10a effectors in MKN45 cells. Furthermore, the underlying mechanism of miR‑10a functions in GC was explored. The findings indicated that miR‑10a‑5p directly targets MAPK8IP1, as a major mechanism for gastric cancer metastasis. The results of the present study suggested that miR‑10a may be a potential target for the treatment of GC in the future.

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	Wakamatsu Y, Sakamoto N, Oo HZ, Naito Y, Uraoka N, Anami K, Sentani K, Oue N and Yasui W: Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int. 62:112–119. 2012. View Article : Google Scholar : PubMed/NCBI
3	Hsu KW, Hsieh RH, Huang KH, Fen-Yau Li A, Chi CW, Wang TY, Tseng MJ, Wu KJ and Yeh TS: Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression. Carcinogenesis. 33:1459–1467. 2012. View Article : Google Scholar : PubMed/NCBI
4	Takano Y, Kato Y, Masuda M, Ohshima Y and Okayasu I: Cyclin D2, but not cyclin D1, overexpression closely correlates with gastric cancer progression and prognosis. J Pathol. 189:194–200. 1999. View Article : Google Scholar : PubMed/NCBI
5	Maruyama K, Gunvén P, Okabayashi K, Sasako M and Kinoshita T: Lymph node metastases of gastric cancer. General pattern in 1931 patients. Ann Surg. 210:596–602. 1989. View Article : Google Scholar : PubMed/NCBI
6	Qu JL, Qu XJ, Zhao MF, Teng YE, Zhang Y, Hou KZ, Jiang YH, Yang XH and Liu YP: Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis. 41:875–880. 2009. View Article : Google Scholar : PubMed/NCBI
7	Mulholland DJ, Kobayashi N, Ruscetti M, Zhi A, Tran LM, Huang J, Gleave M and Wu H: Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res. 72:1878–1889. 2012. View Article : Google Scholar : PubMed/NCBI
8	Davis RJ: Signal transduction by the JNK group of MAP kinases. Cell. 103:239–252. 2000. View Article : Google Scholar : PubMed/NCBI
9	Thompson NA, Haefliger JA, Senn A, Tawadros T, Magara F, Ledermann B, Nicod P and Waeber G: Islet-brain1/JNK-interacting protein-1 is required for early embryogenesis in mice. J Biol Chem. 276:27745–27748. 2001. View Article : Google Scholar : PubMed/NCBI
10	Crew KD and Neugut AI: Epidemiology of gastric cancer. World J Gastroenterol. 12:354–362. 2006. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
12	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
13	Cao M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, Noro R, Yoshimura A, Cai L and Gemma A: MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol. 41:869–875. 2012.PubMed/NCBI
14	Pacurari M, Addison JB, Bondalapati N, Wan YW, Luo D, Qian Y, Castranova V, Ivanov AV and Guo NL: The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells. Int J Oncol. 43:548–560. 2013.PubMed/NCBI
15	Verdoodt B, Neid M, Vogt M, Kuhn V, Liffers ST, Palisaar RJ, Noldus J, Tannapfel A and Mirmohammadsadegh A: MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer. Int J Oncol. 43:307–314. 2013.PubMed/NCBI
16	Wang P, Zou F, Zhang X, Li H, Dulak A, Tomko RJ Jr, Lazo JS, Wang Z, Zhang L and Yu J: microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 69:8157–8165. 2009. View Article : Google Scholar : PubMed/NCBI
17	Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, et al: A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 353:1793–1801. 2005. View Article : Google Scholar : PubMed/NCBI
18	Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H, Liedberg F, Chebil G, Gudjonsson S, Borg A, et al: MiRNA expression in urothelial carcinomas: Important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer. 124:2236–2242. 2009. View Article : Google Scholar : PubMed/NCBI
19	Ujifuku K, Mitsutake N, Takakura S, Matsuse M, Saenko V, Suzuki K, Hayashi K, Matsuo T, Kamada K, Nagata I and Yamashita S: miR-195, miR-455-3p and miR-10a (*) are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. Cancer Lett. 296:241–248. 2010. View Article : Google Scholar : PubMed/NCBI
20	Ohuchida K, Mizumoto K, Lin C, Yamaguchi H, Ohtsuka T, Sato N, Toma H, Nakamura M, Nagai E, Hashizume M and Tanaka M: MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene. Ann Surg Oncol. 19:2394–2402. 2012. View Article : Google Scholar : PubMed/NCBI
21	Weiss FU, Marques IJ, Woltering JM, Vlecken DH, Aghdassi A, Partecke LI, Heidecke CD, Lerch MM and Bagowski CP: Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer. Gastroenterology. 137:2136–2145.e1-7. 2009. View Article : Google Scholar : PubMed/NCBI
22	Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW and Weinberg RA: Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 28:341–347. 2010. View Article : Google Scholar : PubMed/NCBI
23	Chen W, Tang Z, Sun Y, Zhang Y, Wang X, Shen Z, Liu F and Qin X: miRNA expression profile in primary gastric cancers and paired lymph node metastases indicates that miR-10a plays a role in metastasis from primary gastric cancer to lymph nodes. Exp Ther Med. 3:351–356. 2012.PubMed/NCBI
24	Novák J and Fabian P: Comments on the TNM classification of malignant tumours - 7th edition. Klin Onkol. 24:149–150. 2011.(In Czech). PubMed/NCBI
25	Brabletz T, Jung A, Spaderna S, Hlubek F and Kirchner T: Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer. 5:744–749. 2005. View Article : Google Scholar : PubMed/NCBI
26	Liu J, Zhang Y, Xu R, Du J, Hu Z, Yang L, Chen Y, Zhu Y and Gu L: PI3K/Akt-dependent phosphorylation of GSK3β and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration. Cell Signal. 25:447–456. 2013. View Article : Google Scholar : PubMed/NCBI
27	Zhang Z, Liu S, Shi R and Zhao G: miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition. Cancer Genet. 204:486–491. 2011. View Article : Google Scholar : PubMed/NCBI
28	Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, Sun L, Ji G, Shi Y, Han Z, et al: miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 9:824–833. 2011. View Article : Google Scholar : PubMed/NCBI
29	Cai L, Li J, Zhang X, Lu Y, Wang J, Lyu X, Chen Y, Liu J, Cai H, Wang Y and Li X: Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma. Oncotarget. 6:7838–7850. 2015. View Article : Google Scholar : PubMed/NCBI
30	Doll R and Peto R: The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst. 66:1191–1308. 1981.PubMed/NCBI
31	Harding TC, Xue L, Bienemann A, Haywood D, Dickens M, Tolkovsky AM and Uney JB: Inhibition of JNK by overexpression of the JNL binding domain of MAPK8IP1 prevents apoptosis in sympathetic neurons. J Biol Chem. 276:4531–4534. 2001. View Article : Google Scholar : PubMed/NCBI
32	Saunders MA, Liang H and Li WH: Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA. 104:3300–3305. 2007. View Article : Google Scholar : PubMed/NCBI
33	Li D, Qu X, Hou K, Zhang Y, Dong Q, Teng Y, Zhang J and Liu Y: PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs. 20:59–64. 2009. View Article : Google Scholar : PubMed/NCBI
34	Xie X, Tang B, Zhou J, Gao Q and Zhang P: Inhibition of the PI3K/Akt pathway increases the chemosensitivity of gastric cancer to vincristine. Oncol Rep. 30:773–782. 2013.PubMed/NCBI
35	Liu J, Liu Q, Wan Y, Zhao Z, Yu H, Luo H and Tang Z: Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K. Int J Oncol. 45:282–290. 2014.PubMed/NCBI