CMIP is oncogenic in human gastric cancer cells

Zhang,Jianlin; Huang,Jin; Wang,Xingyu; Chen,Weidong; Tang,Qinqing; Fang,Maoyong; Qian,Yeben

doi:10.3892/mmr.2017.7541

CMIP is oncogenic in human gastric cancer cells

Authors:
- Jianlin Zhang
- Jin Huang
- Xingyu Wang
- Weidong Chen
- Qinqing Tang
- Maoyong Fang
- Yeben Qian
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Affiliations: Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Pathology, The Second People's Hospital of Hefei, Hefei, Anhui 230011, P.R. China, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
Published online on: September 20, 2017 https://doi.org/10.3892/mmr.2017.7541
Pages: 7277-7286
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma. c‑Maf inducing protein (CMIP) is involved in the c‑Maf signaling pathway, which was reported to serve an important role in human minimal change nephrotic syndrome and in human reading and language related behavior. However, the relationship between CMIP and human gastric cancer has not yet been reported. In the present study, CMIP protein levels in gastric cancer tissues and cells were measured using immunohistochemistry and western blot analysis; the expression of CMIP protein was significantly higher in gastric cancer tissues compared with normal gastric tissues. Expression was positively associated with poorer clinical parameters, relapse‑free survival and overall survival. Furthermore, using cell counting, Cell Counting Kit‑8, colony formation, wound healing and Transwell assays, together with flow cytometry, CMIP depletion by RNA interference was observed to reduce the capacity of gastric cancer cells to proliferate and migrate in vitro. Furthermore, the upstream and downstream genes of CMIP were analyzed by luciferase reporter assay and reverse transcription quantitative polymerase chain reaction, which indicated that CMIP was a direct target of miR‑101‑3p. In addition, CMIP knockdown was observed to result in the downregulation of MDM2 and mitogen activated protein kinase (MAPK) expression at the mRNA level. In conclusion, CMIP demonstrated an oncogenic role in human gastric cancer cells. Furthermore, microRNA‑101‑3p, MDM2 and MAPK were involved in the CMIP signaling pathway in gastric cancer. CMIP could be a novel target for further investigation in the clinical therapeutic management of gastric cancer.

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1	Lee KB, Jin H, Ye S, Park BH and Kim SM: Recombinant human bone morphogenetic protein-2 inhibits gastric cancer cell proliferation by inactivating Wnt signaling pathway via c-Myc with aurora kinases. Oncotarget. 7:73473–73485. 2016.PubMed/NCBI
2	Yin K, Liu M, Zhang M, Wang F, Fen M, Liu Z, Yuan Y, Gao S, Yang L, Zhang W, et al: miR-208a-3p suppresses cell apoptosis by targeting PDCD4 in gastric cancer. Oncotarget. 7:67321–67332. 2016. View Article : Google Scholar : PubMed/NCBI
3	Scott RB, Harrison J, Boulton C, Wilson J, Gregory R, Parkin S, Bain PG, Joint C, Stein J and Aziz TZ: Global attentional-executive sequelae following surgical lesions to globus pallidus interna. Brain. 125:562–574. 2002. View Article : Google Scholar : PubMed/NCBI
4	Feng T, Sun L, Qi W, Pan F, Lv J, Guo J, Zhao S, Ding A and Qiu W: Prognostic significance of Tspan9 in gastric cancer. Mol Clin Oncol. 5:231–236. 2016. View Article : Google Scholar : PubMed/NCBI
5	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
6	Zakko L, Lutzke L and Wang KK: Screening and preventive strategies in esophagogastric cancer. Surg Oncol Clin N Am. 26:163–178. 2017. View Article : Google Scholar : PubMed/NCBI
7	Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, et al: Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 24:4991–4997. 2006. View Article : Google Scholar : PubMed/NCBI
8	Murakami Y, Yatabe Y, Sakaguchi T, Sasaki E, Yamashita Y, Morito N, Yoh K, Fujioka Y, Matsuno F, Hata H, et al: c-Maf expression in angioimmunoblastic T-cell lymphoma. Am J Surg Pathol. 31:1695–1702. 2007. View Article : Google Scholar : PubMed/NCBI
9	Benkhelifa S, Provot S, Nabais E, Eychéne A, Calothy G and Felder-Schmittbuhl MP: Phosphorylation of MafA Is essential for its transcriptional and biological properties. Mol Cell Biol. 21:4441–4452. 2001. View Article : Google Scholar : PubMed/NCBI
10	Szymańska K, Szczałuba K, Lugowska A, Obersztyn E, Radkowski M, Nowakowska BA, Kuśmierska K, Tryfon J and Demkow U: The analysis of genetic aberrations in children with inherited neurometabolic and neurodevelopmental disorders. Biomed Res Int. 2014:4247962014. View Article : Google Scholar : PubMed/NCBI
11	Newbury DF, Winchester L, Addis L, Paracchini S, Buckingham LL, Clark A, Cohen W, Cowie H, Dworzynski K, Everitt A, et al: CMIP and ATP2C2 modulate phonological short-term memory in language impairment. Am J Hum Genet. 85:264–272. 2009. View Article : Google Scholar : PubMed/NCBI
12	Grimbert P, Valanciute A, Audard V, Pawlak A, Le Gouvelo S, Lang P, Niaudet P, Bensman A, Guellaën G and Sahali D: Truncation of C-mip (Tc-mip), a new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization. J Exp Med. 198:797–807. 2003. View Article : Google Scholar : PubMed/NCBI
13	Audard V, Zhang SY, Copie-Bergman C, Rucker-Martin C, Ory V, Candelier M, Baia M, Lang P, Pawlak A and Sahali D: Occurrence of minimal change nephrotic syndrome in classical Hodgkin lymphoma is closely related to the induction of c-mip in Hodgkin-Reed Sternberg cells and podocytes. Blood. 115:3756–3762. 2010. View Article : Google Scholar : PubMed/NCBI
14	Liu Y, Su L, Lin Q, Han Y, You P and Fan Q: Induction of C-Mip by IL-17 plays an important role in Adriamycin-induced Podocyte damage. Cell Physiol Biochem. 36:1274–1290. 2015. View Article : Google Scholar : PubMed/NCBI
15	Ory V, Fan Q, Hamdaoui N, Zhang SY, Desvaux D, Audard V, Candelier M, Noel LH, Lang P, Guellaën G, et al: c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes. Am J Pathol. 180:2284–2292. 2012. View Article : Google Scholar : PubMed/NCBI
16	Scerri TS, Morris AP, Buckingham LL, Newbury DF, Miller LL, Monaco AP, Bishop DV and Paracchini S: DCDC2, KIAA0319 and CMIP are associated with reading-related traits. Biol Psychiatry. 70:237–245. 2011. View Article : Google Scholar : PubMed/NCBI
17	Fletcher CDM, Unni KK and Meretens F: Pathology and Genetics of Tumours of Soft Tissue and BoneWorld Health Organization Classification of Tumors. IARC Press; Lyon: 2002
18	Ding K, Wu Z, Wang N, Wang X, Wang Y, Qian P, Meng G and Tan S: MiR-26a performs converse roles in proliferation and metastasis of different gastric cancer cells via regulating of PTEN expression. Pathol Res Pract. 213:467–475. 2017. View Article : Google Scholar : PubMed/NCBI
19	Capes-Davis A, Theodosopoulos G, Atkin I, Drexler HG, Kohara A, MacLeod RA, Masters JR, Nakamura Y, Reid YA, Reddel RR, et al: 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
20	Jiang T, Zhao B, Li X and Wan J: ARPP-19 promotes proliferation and metastasis of human glioma. Neuroreport. 27:960–966. 2016. View Article : Google Scholar : PubMed/NCBI
21	Ding ZY, Jin GN, Wang W, Chen WX, Wu YH, Ai X, Chen L, Zhang WG, Liang HF, Laurence A, et al: Reduced expression of transcriptional intermediary factor 1 gamma promotes metastasis and indicates poor prognosis of hepatocellular carcinoma. Hepatology. 60:1620–1636. 2014. View Article : Google Scholar : PubMed/NCBI
22	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
23	Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T, Bergsagel PL, Kuehl WM and Staudt LM: Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer Cell. 5:191–199. 2004. View Article : Google Scholar : PubMed/NCBI
24	Nip H, Dar AA, Saini S, Colden M, Varahram S, Chowdhary H, Yamamura S, Mitsui Y, Tanaka Y, Kato T, et al: Oncogenic microRNA-4534 regulates PTEN pathway in prostate cancer. Oncotarget. 7:68371–68384. 2016. View Article : Google Scholar : PubMed/NCBI
25	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
26	Yoo HI, Kim BK and Yoon SK: MicroRNA-330-5p negatively regulates ITGA5 expression in human colorectal cancer. Oncol Rep. 36:3023–3029. 2016. View Article : Google Scholar : PubMed/NCBI
27	Zhang Y, Peng Z, Zhao Y and Chen L: microRNA-25 inhibits cell apoptosis of human gastric adenocarcinoma cell line AGS via regulating CCNE1 and MYC. Med Sci Monit. 22:1415–1420. 2016. View Article : Google Scholar : PubMed/NCBI
28	Xin R, Bai F, Feng Y, Jiu M, Liu X, Bai F, Nie Y and Fan D: MicroRNA-214 promotes peritoneal metastasis through regulating PTEN negatively in gastric cancer. Clin Res Hepatol Gastroenterol. 40:748–754. 2016. View Article : Google Scholar : PubMed/NCBI
29	Li W, Zhang J, Chen T, Yin P, Yang J and Cao Y: miR-132 upregulation promotes gastric cancer cell growth through suppression of FoxO1 translation. Tumour Biol. Aug 23–2015.(Epub ahead of print).
30	Wang Y, Zeng J, Pan J, Geng X, Li L, Wu J, Song P, Wang Y, Liu J and Wang L: MiR-320a inhibits gastric carcinoma by targeting activity in the FoxM1-P27KIP1 axis. Oncotarget. 7:29275–29286. 2016. View Article : Google Scholar : PubMed/NCBI
31	Xu C, Li M, Zhang L, Bi Y, Wang P, Li J and Jiang X: MicroRNA-205 suppresses the invasion and epithelial-mesenchymal transition of human gastric cancer cells. Mol Med Rep. 13:4767–4773. 2016. View Article : Google Scholar : PubMed/NCBI
32	Tsai MM, Huang HW, Wang CS, Lee KF, Tsai CY, Lu PH, Chi HC, Lin YH, Kuo LM and Lin KH: MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer. Oncotarget. 7:39511–39526. 2016. View Article : Google Scholar : PubMed/NCBI
33	Liu P, Ye F and Xie X, Li X, Tang H, Li S, Huang X, Song C, Wei W and Xie X: mir-101-3p is a key regulator of tumor metabolism in triple negative breast cancer targeting AMPK. Oncotarget. 7:35188–35198. 2016. View Article : Google Scholar : PubMed/NCBI
34	Liu XY, Liu ZJ, He H, Zhang C and Wang YL: MicroRNA-101-3p suppresses cell proliferation, invasion and enhances chemotherapeutic sensitivity in salivary gland adenoid cystic carcinoma by targeting Pim-1. Am J Cancer Res. 5:3015–3029. 2015.PubMed/NCBI
35	Sheng Y, Li J, Zou C, Wang S, Cao Y, Zhang J, Huang A and Tang H: Downregulation of miR-101-3p by hepatitis B virus promotes proliferation and migration of hepatocellular carcinoma cells by targeting Rab5a. Arch Virol. 159:2397–2410. 2014. View Article : Google Scholar : PubMed/NCBI
36	Cui W, Wu R, Cao H, Gao J, Wang X and Ren Q: P53 gene mutation and expression of MDM2, P53, P16 protein and their relationship in human glioma. J Huazhong Univ Sci Technolog Med Sci. 25:622–624, 635. 2005. View Article : Google Scholar : PubMed/NCBI
37	Danilovskyi SV, Minchenko DO, Moliavko OS, Kovalevska OV, Karbovskyi LL and Minchenko OH: ERN1 knockdown modifies the hypoxic regulation of TP53, MDM2, USP7 and PERP gene expressions in U87 glioma cells. Ukr Biochem J. 86:90–102. 2014. View Article : Google Scholar : PubMed/NCBI
38	Shen J, Niu W, Zhou M and Zhang H, Ma J, Wang L and Zhang H: MicroRNA-410 suppresses migration and invasion by targeting MDM2 in gastric cancer. PLoS One. 9:e1045102014. View Article : Google Scholar : PubMed/NCBI
39	Wang BY, Cao J, Chen JW and Liu QY: Triptolide induces apoptosis of gastric cancer cells via inhibiting the overexpression of MDM2. Med Oncol. 31:2702014. View Article : Google Scholar : PubMed/NCBI
40	Saji S, Nakashima S, Hayashi S, Toi M, Saji S and Nozawa Y: Overexpression of MDM2 in MCF-7 promotes both growth advantage and p53 accumulation in response to estradiol. Jpn J Cancer Res. 90:210–218. 1999. View Article : Google Scholar : PubMed/NCBI
41	Hai J, Sakashita S, Allo G, Ludkovski O, Ng C, Shepherd FA and Tsao MS: Inhibiting MDM2-p53 interaction suppresses tumor growth in patient-derived non-small cell lung cancer Xenograft models. J Thorac Oncol. 10:1172–1180. 2015. View Article : Google Scholar : PubMed/NCBI
42	Wei L, Li Y and Suo Z: TSPAN8 promotes gastric cancer growth and metastasis via ERK MAPK pathway. Int J Clin Exp Med. 8:8599–8607. 2015.PubMed/NCBI
43	Yang M, Gu YY, Peng H, Zhao M, Wang J, Huang SK, Yuan XH, Li J, Sang JL, Luo Q and Huang C: NAIF1 inhibits gastric cancer cells migration and invasion via the MAPK pathways. J Cancer Res Clin Oncol. 141:1037–1047. 2015. View Article : Google Scholar : PubMed/NCBI
44	Zhao M, Howard EW, Parris AB, Guo Z, Zhao Q and Yang X: Alcohol promotes migration and invasion of triple-negative breast cancer cells through activation of p38 MAPK and JNK. Mol Carcinog. 56:849–862. 2017. View Article : Google Scholar : PubMed/NCBI
45	Kim GT, Lee SH and Kim YM: Torilis japonica extract-generated intracellular ROS induces apoptosis by reducing the mitochondrial membrane potential via regulation of the AMPK-p38 MAPK signaling pathway in HCT116 colon cancer. Int J Oncol. 49:1088–1098. 2016.PubMed/NCBI
46	Peng W and Fan H: Long noncoding RNA CCHE1 indicates a poor prognosis of hepatocellular carcinoma and promotes carcinogenesis via activation of the ERK/MAPK pathway. Biomed Pharmacother. 83:450–455. 2016. View Article : Google Scholar : PubMed/NCBI
47	Yokozaki H: Molecular characteristics of eight gastric cancer cell lines established in Japan. Pathol Int. 50:767–777. 2000. View Article : Google Scholar : PubMed/NCBI