Downregulation of RPN2 induces apoptosis and inhibits migration and invasion in colon carcinoma

Bi,Chongyao; Jiang,Baofei

doi:10.3892/or.2018.6434

Downregulation of RPN2 induces apoptosis and inhibits migration and invasion in colon carcinoma

Authors:
- Chongyao Bi
- Baofei Jiang
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Affiliations: Department of General Surgery, Jiaozhou Central Hospital of Qingdao, Qingdao, Shandong 266300, P.R. China, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: May 10, 2018 https://doi.org/10.3892/or.2018.6434
Pages: 283-293
Copyright: © Bi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The morbidity of colorectal cancer (CRC) increases annualy, which accounts to higher mortality worldwide. Therefore, it is important to study the pathogenesis of colon cancer. Ribophorin II (RPN2), part of the N-oligosaccharyltransferase complex, is highly expressed in CRC. In the present study, we investigated whether RPN2 can regulate apoptosis, migration and invasion by RNA interference in CRC and sought to clarify the molecular mechanism involved. Based on previous research, an abnormal high expression of RPN2 was observed in CRC tissues and cell lines by real-time (RT)-PCR, immunohistochemistry (IHC) and western blot analysis. RPN2 knockdown via small RNA interference (siRNA) strategy attenuated the expression of RPN2 at the mRNA and protein levels in vivo, leading to decreased cell viability and increased cell apoptosis. In addition, RNAi-RPN2 effectively arrested the cell cycle at the G0/G1-phase in SW1116 and SW480 cells. Furthermore, the Transwell assay demonstrated that cell migration and invasion abilities were significantly inhibited after cell transfection with RPN2 interference plasmid. The apoptosis-related protein (caspase-3) expression was increased and the cell cycle-related protein (cyclin D1) expression was decreased in the siRNA-RPN2 group. RT-PCR and western blot analysis results indicated that migration- and invasion-related proteins including E-cadherin, matrix metalloproteinases (MMP)-2 and TIMP-2 were markedly regulated by RPN2 siRNA. Phosphorylation levels of signal transducer and activator of transcription (STAT)3 and Janus kinase (JAK)2 were inhibited by RPN2 siRNA. These findings indicated a novel pathway of tumor-promoting activity by RPN2 in CRC, with significant implications for unraveling the tumorigenesis of CRC.

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1	Niknami Z, Eslamifar A, Emamirazavi A, Ebrahimi A and Shirkoohi R: The association of vimentin and fibronectin gene expression with epithelial-mesenchymal transition and tumor malignancy in colorectal carcinoma. EXCLI J. 16:1009–1017. 2017.PubMed/NCBI
2	Xu RH, Shen L, Li J, Xu JM, Bi F, Ba Y, Bai L, Shu YQ, Liu TS, Li YH, et al: Expert consensus on maintenance treatment for metastatic colorectal cancer in China. Chin J Cancer. 35:132016. View Article : Google Scholar : PubMed/NCBI
3	Shin CM, Han K, Lee DH, Choi YJ, Kim N, Park YS and Yoon H: Association among obesity, metabolic health, and the risk for colorectal cancer in the general population in Korea using the National Health Insurance Service-National Sample Cohort. Dis Colon Rectum. 60:1192–1200. 2017. View Article : Google Scholar : PubMed/NCBI
4	Lopes-Ramos CM, Barros BP, Koyama FC, Carpinetti PA, Pezuk J, Doimo NT, Habr-Gama A, Perez RO and Parmigiani RB: E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer. PLoS One. 12:e01811532017. View Article : Google Scholar : PubMed/NCBI
5	Jayasekara H, English DR, Haydon A, Hodge AM, Lynch BM, Rosty C, Williamson EJ, Clendenning M, Southey MC1, Jenkins MA, et al: Associations of alcohol intake, smoking, physical activity and obesity with survival following colorectal cancer diagnosis by stage, anatomic site and tumor molecular subtype. Int J Cancer. 142:238–250. 2018. View Article : Google Scholar : PubMed/NCBI
6	Altobelli E, Latella G, Morroni M, Licini C, Tossetta G, Mazzucchelli R, Profeta VF, Coletti G, Leocata P, Castellucci M, et al: Low HtrA1 expression in patients with long standing ulcerative colitis and colorectal cancer. Oncol Rep. 38:418–426. 2017. View Article : Google Scholar : PubMed/NCBI
7	Nandra R, Parry M, Forsberg J and Grimer R: Can a bayesian belief network be used to estimate 1-year survival in patients with bone sarcomas? Clin Orthop Relat Res. 475:1681–1689. 2017. View Article : Google Scholar : PubMed/NCBI
8	Yogarajah M and Tefferi A: Leukemic transformation in myeloproliferative neoplasms: A literature review on risk, characteristics, and outcome. Mayo Clin Proc. 92:1118–1128. 2017. View Article : Google Scholar : PubMed/NCBI
9	Fujieda Y, Amengual O, Matsumoto M, Kuroki K, Takahashi H, Kono M, Kurita T, Otomo K, Kato M, Oku K, et al: Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes. Rheumatology (Oxford). 55:1117–1126. 2016. View Article : Google Scholar : PubMed/NCBI
10	Ono M, Tsuda H, Kobayashi T, Takeshita F, Takahashi RU, Tamura K, Akashi-Tanaka S, Moriya T, Yamasaki T, Kinoshita T, et al: The expression and clinical significance of ribophorin II (RPN2) in human breast cancer. Pathol Int. 65:301–308. 2015. View Article : Google Scholar : PubMed/NCBI
11	Honma K, Iwao-Koizumi K, Takeshita F, Yamamoto Y, Yoshida T, Nishio K, Nagahara S, Kato K and Ochiya T: RPN2 gene confers docetaxel resistance in breast cancer. Nat Med. 14:939–948. 2008. View Article : Google Scholar : PubMed/NCBI
12	Tominaga N, Hagiwara K, Kosaka N, Honma K, Nakagama H and Ochiya T: RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy. Mol Cancer. 13:1342014. View Article : Google Scholar : PubMed/NCBI
13	Kurashige J, Watanabe M, Iwatsuki M, Kinoshita K, Saito S, Nagai Y, Ishimoto T, Baba Y, Mimori K and Baba H: RPN2 expression predicts response to docetaxel in oesophageal squamous cell carcinoma. Br J Cancer. 107:1233–1238. 2012. View Article : Google Scholar : PubMed/NCBI
14	Fujiwara T, Takahashi RU, Kosaka N, Nezu Y, Kawai A, Ozaki T and Ochiya T: RPN2 gene confers osteosarcoma cell malignant phenotypes and determines clinical prognosis. Mol Ther Nucleic Acids. 3:e1892014. View Article : Google Scholar : PubMed/NCBI
15	Yuan TM, Liang RY, Chueh PJ and Chuang SM: Role of ribophorin II in the response to anticancer drugs in gastric cancer cell lines. Oncol Lett. 9:1861–1868. 2015. View Article : Google Scholar : PubMed/NCBI
16	Loo LW, Tiirikainen M, Cheng I, Lum-Jones A, Seifried A, Church JM, Gryfe R, Weisenberger DJ, Lindor NM, Gallinger S, et al: Integrated analysis of genome-wide copy number alterations and gene expression in microsatellite stable, CpG island methylator phenotype-negative colon cancer. Genes Chromosomes Cancer. 52:450–466. 2013. View Article : Google Scholar : PubMed/NCBI
17	Ju KD, Lim JW and Kim H: Peroxisome proliferator-activated receptor-gamma inhibits the activation of STAT3 in cerulein-stimulated pancreatic acinar cells. J Cancer Prev. 22:189–194. 2017. View Article : Google Scholar : PubMed/NCBI
18	Kim EY, Jung JY, Kim A, Chang YS and Kim SK: ABT-737 synergizes with cisplatin bypassing aberration of apoptotic pathway in non-small cell lung cancer. Neoplasia. 19:354–363. 2017. View Article : Google Scholar : PubMed/NCBI
19	Huang SN, Ruan HZ, Chen MY, Zhou G and Qian ZM: Aspirin increases ferroportin 1 expression by inhibiting hepcidin via the JAK/STAT3 pathway in interleukin 6-treated PC-12 cells. Neurosci Lett. 662:1–5. 2018. View Article : Google Scholar : PubMed/NCBI
20	Sun Y, Zhou P, Chen S, Hu C, Bai Q, Wu H, Chen Y, Zhou P, Zeng X, Liu Z, et al: The JAK/STAT3 signaling pathway mediates inhibition of host cell apoptosis by Chlamydia psittaci infection. Pathog Dis. Aug 3–2017.(Epub ahead of print). doi: 10.1093/femsle/ftx088. View Article : Google Scholar : PubMed/NCBI
21	Wang J, Xu J and Xing G: Lycorine inhibits the growth and metastasis of breast cancer through the blockage of STAT3 signaling pathway. Acta Biochim Biophys Sin (Shanghai). 49:771–779. 2017. View Article : Google Scholar : PubMed/NCBI
22	Berthenet K, Bokhari A, Lagrange A, Marcion G, Boudesco C, Causse S, De Thonel A, Svrcek M, Goloudina AR, Dumont S, et al: HSP110 promotes colorectal cancer growth through STAT3 activation. Oncogene. 36:2328–2336. 2017. View Article : Google Scholar : PubMed/NCBI
23	Yan Y, Su C, Hang M, Huang H, Zhao Y, Shao X and Bu X: Recombinant Newcastle disease virus rL-RVG enhances the apoptosis and inhibits the migration of A549 lung adenocarcinoma cells via regulating alpha 7 nicotinic acetylcholine receptors in vitro. Virol J. 14:1902017. View Article : Google Scholar : PubMed/NCBI
24	Luo JM, Cao FL, Meng C, Lin LJ, Ma SQ, Peng SH, Gao HL, Javidiparsijani S, Wang GR, Zhang ML, et al: Clinicopathological and molecular characteristics of synchronous gastric adenocarcinoma and gastrointestinal stromal tumors. Sci Rep. 7:128902017. View Article : Google Scholar : PubMed/NCBI
25	Naine SJ, Devi CS, Mohanasrinivasan V, Doss CG and Kumar DT: Binding and molecular dynamic studies of sesquiterpenes (2R-acetoxymethyl-1,3,3-trimethyl-4t-(3-methyl-2-buten-1-yl)-1t-cyclohexanol) derived from marine Streptomyces sp. VITJS8 as potential anticancer agent. Appl Microbiol Biotechnol. 100:2869–2882. 2016. View Article : Google Scholar : PubMed/NCBI
26	Li T, Ding ZL, Zheng YL and Wang W: MiR-484 promotes non-small-cell lung cancer (NSCLC) progression through inhibiting Apaf-1 associated with the suppression of apoptosis. Biomed Pharmacother. 96:153–164. 2017. View Article : Google Scholar : PubMed/NCBI
27	Taira J, Sonamoto M and Uehara M: Dual biological functions of a cytoprotective effect and apoptosis induction by bioavailable marine carotenoid fucoxanthinol through modulation of the Nrf2 activation in RAW264.7 macrophage cells. Mar Drugs. 15:E3052017. View Article : Google Scholar : PubMed/NCBI
28	Zhao Q, Li M, Chen M, Zhou L, Zhao L, Hu R, Yan R and Dai K: Lovastatin induces platelet apoptosis. Environ Toxicol Pharmacol. 42:69–75. 2016. View Article : Google Scholar : PubMed/NCBI
29	Hazama Y, Moriya T, Sugihara M, Sano R, Shiota M, Nakamura T and Shimoya K: The analysis of cell cycle-related proteins in ovarian clear cell carcinoma versus high-grade serous carcinoma. Int J Gynecol Pathol. Oct 10–2017.(Epub ahead of print). doi: 10.1097/PGP.0000000000000461. View Article : Google Scholar : PubMed/NCBI
30	Wang X, Li Y, Lin M, Jin J and Huang Z: Rhodium (II) complex with 2-benzoylpyridine, a novel potential chemotherapeutic drug, induces cell cycle arrest and apoptosis in HepG2 cells. Biometals. 30:903–915. 2017. View Article : Google Scholar : PubMed/NCBI
31	He S, Liao B, Deng Y, Su C, Tuo J, Liu J, Yao S and Xu L: MiR-216b inhibits cell proliferation by targeting FOXM1 in cervical cancer cells and is associated with better prognosis. BMC Cancer. 17:6732017. View Article : Google Scholar : PubMed/NCBI
32	Liu L, Zhang C, Li X, Sun W, Qin S, Qin L and Wang X: miR-223 promotes colon cancer by directly targeting p120 catenin. Oncotarget. 8:63764–63779. 2017.PubMed/NCBI
33	Liu H, Zhen Q and Fan Y: LncRNA GHET1 promotes esophageal squamous cell carcinoma cells proliferation and invasion via induction of EMT. Int J Biol Markers. 32:e403–e408. 2017. View Article : Google Scholar : PubMed/NCBI
34	Pisamai S, Rungsipipat A, Kunnasut N and Suriyaphol G: Immunohistochemical expression profiles of cell adhesion molecules, matrix metalloproteinases and their tissue inhibitors in central and peripheral neoplastic foci of feline mammary carcinoma. J Comp Pathol. 157:150–162. 2017. View Article : Google Scholar : PubMed/NCBI
35	Ohba S, Lanigan TM and Roessler BJ: Leptin receptor JAK2/STAT3 signaling modulates expression of Frizzled receptors in articular chondrocytes. Osteoarthritis Cartilage. 18:1620–1629. 2010. View Article : Google Scholar : PubMed/NCBI
36	Li W, Zhang H, Nie M, Tian Y, Chen X, Chen C, Chen H and Liu R: Ursolic acid derivative FZU-03,010 inhibits STAT3 and induces cell cycle arrest and apoptosis in renal and breast cancer cells. Acta Biochim Biophys Sin (Shanghai). 49:367–373. 2017. View Article : Google Scholar : PubMed/NCBI
37	Zhou W, Bi X, Gao G and Sun L: miRNA-133b and miRNA-135a induce apoptosis via the JAK2/STAT3 signaling pathway in human renal carcinoma cells. Biomed Pharmacother. 84:722–729. 2016. View Article : Google Scholar : PubMed/NCBI
38	Zhu L and Ding X: Molecular design of Stat3-derived peptide selectivity between BET proteins Brd2 and Brd4 in ovarian cancer. J Mol Recognit. Oct 6–2017.(Epub ahead of print). doi: 10.1002/jmr.2679.
39	Liu X, Wei W, Li X, Shen P, Ju D, Wang Z, Zhang R, Yang F, Chen C, Cao K, et al: BMI1 and MEL18 promote colitis-associated cancer in mice via REG3B and STAT3. Gastroenterology. 153:1607–1620. 2017. View Article : Google Scholar : PubMed/NCBI