Startseite LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis
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LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis

  • Xuexiu Zhang , Jianning Yao , Haoling Shi , Bing Gao und Lianfeng Zhang EMAIL logo
Veröffentlicht/Copyright: 6. Januar 2019

Abstract

The present study aims to determine the potential biomarkers and uncover the regulatory mechanisms of the long-noncoding RNA (lncRNA) TINCR/miR-107/CD36 axis in colorectal cancer (CRC). Aberrantly-expressed lncRNAs and differential-expressed genes were identified by analyzing the dataset GSE40967. Gene set enrichment analysis was employed, and Cytoscape software helped in establishing the co-expression network between lncRNAs and genes. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis contributes to examining the expression levels of lncRNA TINCR, miR-107 and CD36. The dual luciferase assay was used to validate the association between miR-107 and lncRNA TINCR or CD36. The EdU incorporation assay was employed, and flow cytometry was employed to detect cell apoptosis with the tumor xenograft model being utilized. Significantly dysregulated lncRNAs and mRNAs were identified. The peroxisome proliferator-activated receptor (PPAR) signaling pathway in CRC tissues was down-regulated. The loss of TINCR expression was associated with CRC progression. The expression levels of the TINCR and CD36 were down-regulated. We identified miR-107 as an inhibitory target of TINCR and CD36. Overexpression of TINCR could inhibit cell proliferation and promote apoptosis. MiR-107 overexpression in CRC cells induced proliferation and impeded apoptosis. A regulatory function of the lncRNA TINCR/miR-107/CD36 axis in CRC was revealed. LncRNA TINCR overexpression exerted suppressive influence on CRC progression through modulating the PPAR signaling pathway via the miR-107/CD36 axis.

References

Ayremlou, N., Mozdarani, H., Mowla, S.J., and Delavari, A. (2015). Increased levels of serum and tissue miR-107 in human gastric cancer: correlation with tumor hypoxia. Cancer Biomark. 15, 851–860.10.3233/CBM-150529Suche in Google Scholar PubMed

Benderska, N. and Schneider-Stock, R. (2014). Transcription control of DAPK. Apoptosis 19, 298–305.10.1007/s10495-013-0931-6Suche in Google Scholar PubMed

Borland, M.G., Kehres, E.M., Lee, C., Wagner, A.L., Shannon, B.E., Albrecht, P.P., Zhu, B., Gonzalez, F.J., Peters, J.M. (2018). Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells. Toxicology 404405, 25–32.10.1016/j.tox.2018.05.003Suche in Google Scholar PubMed PubMed Central

Bye, W.A., Ma, C., Nguyen, T.M., Parker, C.E., Jairath, V., and East, J.E. (2018). Strategies for detecting colorectal cancer in patients with inflammatory bowel disease: a cochrane systematic review and meta-analysis. Am. J. Gastroenterol. 113, 1801–1809.10.1038/s41395-018-0354-7Suche in Google Scholar PubMed PubMed Central

Chen, H.Y., Lin, Y.M., Chung, H.C., Lang, Y.D., Lin, C.J., Huang, J., Wang, W.C., Lin, F.M., Chen, Z., Huang, H.D., et al. (2012). miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. Cancer Res. 72, 3631–3641.10.1158/0008-5472.CAN-12-0667Suche in Google Scholar PubMed

Chen, Z., Liu, H., Yang, H., Gao, Y., Zhang, G., and Hu, J. (2017). The long noncoding RNA, TINCR, functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in gastric cancer. Onco Targets. Ther. 10, 3353–3362.10.2147/OTT.S137726Suche in Google Scholar PubMed PubMed Central

Cui, J., Mo, J., Luo, M., Yu, Q., Zhou, S., Li, T., Zhang, Y., and Luo, W. (2015). c-Myc-activated long non-coding RNA H19 downregulates miR-107 and promotes cell cycle progression of non-small cell lung cancer. Int. J. Clin. Exp. Pathol. 8, 12400–12409.Suche in Google Scholar

Gao, T., Wang, M., Xu, L., Wen, T., Liu, J., and An, G. (2016). DCLK1 is up-regulated and associated with metastasis and prognosis in colorectal cancer. J. Cancer Res. Clin. Oncol. 142, 2131–2140.10.1007/s00432-016-2218-0Suche in Google Scholar PubMed

Johnstone, C.N., Smith, Y.E., Cao, Y., Burrows, A.D., Cross, R.S., Ling, X., Redvers, R.P., Doherty, J.P., Eckhardt, B.L., Natoli, A.L., et al. (2015). Functional and molecular characterisation of EO771.LMB tumours, a new C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer. Dis. Model Mech. 8, 237–251.10.1242/dmm.017830Suche in Google Scholar PubMed PubMed Central

Lee, J.J., Drakaki, A., Iliopoulos, D., and Struhl, K. (2012). MiR-27b targets PPARgamma to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells. Oncogene 31, 3818–3825.10.1038/onc.2011.543Suche in Google Scholar PubMed PubMed Central

Lee, S., Eguchi, A., Sakamoto, K., Matsumura, S., Tsuzuki, S., Inoue, K., Masuda, D., Yamashita, S., and Fushiki, T. (2015). A role of CD36 in the perception of an oxidised phospholipid species in mice. Biomed. Res. 36, 303–311.10.2220/biomedres.36.303Suche in Google Scholar PubMed

Li, B.R., Xia, L.Q., Liu, J., Liao, L.L., Zhang, Y., Deng, M., Zhong, H.J., Feng, T.T., He, P.P., and Ouyang, X.P. (2017). miR-758-5p regulates cholesterol uptake via targeting the CD36 3′UTR. Biochem. Biophys. Res. Commun. 494, 384–389.10.1016/j.bbrc.2017.09.150Suche in Google Scholar PubMed

Liu, F., Liu, S., Ai, F., Zhang, D., Xiao, Z., Nie, X., and Fu, Y. (2017). miR-107 promotes proliferation and inhibits apoptosis of colon cancer cells by targeting prostate apoptosis response-4 (Par4). Oncol. Res. 25, 967–974.10.3727/096504016X14803476672380Suche in Google Scholar PubMed PubMed Central

Milone, M.R., Pucci, B., Colangelo, T., Lombardi, R., Iannelli, F., Colantuoni, V., Sabatino, L., and Budillon, A. (2016). Proteomic characterization of peroxisome proliferator-activated receptor-gamma (PPARgamma) overexpressing or silenced colorectal cancer cells unveils a novel protein network associated with an aggressive phenotype. Mol. Oncol. 10, 1344–1362.10.1016/j.molonc.2016.07.006Suche in Google Scholar PubMed PubMed Central

Molina-Pinelo, S., Carnero, A., Rivera, F., Estevez-Garcia, P., Bozada, J.M., Limon, M.L., Benavent, M., Gomez, J., Pastor, M.D., Chaves, M., et al. (2014). MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer. BMC Cancer 14, 656.10.1186/1471-2407-14-656Suche in Google Scholar PubMed PubMed Central

Nath, A., Li, I., Roberts, L.R., and Chan, C. (2015). Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma. Sci. Rep. 5, 14752.10.1038/srep14752Suche in Google Scholar PubMed PubMed Central

Orido, T., Fujino, H., Kawashima, T., and Murayama, T. (2005). A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437, 759–763.10.1038/nature03988Suche in Google Scholar PubMed PubMed Central

Orido, T., Fujino, H., Kawashima, T., and Murayama, T. (2010). Decrease in uptake of arachidonic acid by indomethacin in LS174T human colon cancer cells; a novel cyclooxygenase-2-inhibition-independent effect. Arch. Biochem. Biophys. 494, 78–85.10.1016/j.abb.2009.11.025Suche in Google Scholar PubMed

Peng, X.P., Huang, L., and Liu, Z.H. (2016). miRNA-133a attenuates lipid accumulation via TR4-CD36 pathway in macrophages. Biochimie 127, 79–85.10.1016/j.biochi.2016.04.012Suche in Google Scholar PubMed

Peters, J.M., Foreman, J.E., and Gonzalez, F.J. (2011). Dissecting the role of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in colon, breast, and lung carcinogenesis. Cancer Metastasis. Rev. 30, 619–640.10.1007/s10555-011-9320-1Suche in Google Scholar PubMed PubMed Central

Peters, J.M., Shah, Y.M., and Gonzalez, F.J. (2012). The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat. Rev. Cancer 12, 181–195.10.1038/nrc3214Suche in Google Scholar PubMed PubMed Central

Qin, S.B., Peng, D.Y., Lu, J.M., and Ke, Z.P. (2017). MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4. J. Cell Physiol. 233, 6630–6637.10.1002/jcp.26389Suche in Google Scholar PubMed

Rachidi, S.M., Qin, T., Sun, S., Zheng, W.J., and Li, Z. (2013). Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker. PLoS One 8, e57911.10.1371/journal.pone.0057911Suche in Google Scholar PubMed PubMed Central

Reka, A.K., Kurapati, H., Narala, V.R., Bommer, G., Chen, J., Standiford, T.J., and Keshamouni, V.G. (2010). Peroxisome proliferator-activated receptor-gamma activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesenchymal transition. Mol. Cancer Ther. 9, 3221–3232.10.1158/1535-7163.MCT-10-0570Suche in Google Scholar PubMed PubMed Central

Ren, B., Best, B., Ramakrishnan, D.P., Walcott, B.P., Storz, P., and Silverstein, R.L. (2016). LPA/PKD-1-FoxO1 signaling axis mediates endothelial cell CD36 transcriptional repression and proangiogenic and proarteriogenic reprogramming. Arterioscler. Thromb. Vasc. Biol. 36, 1197–1208.10.1161/ATVBAHA.116.307421Suche in Google Scholar PubMed PubMed Central

Santhanam, S., Alvarado, D.M., and Ciorba, M.A. (2016). Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer. Transl. Res. 167, 67–79.10.1016/j.trsl.2015.07.003Suche in Google Scholar PubMed PubMed Central

Schmoll, H.J., Arnold, D., de Gramont, A., Ducreux, M., Grothey, A., O’Dwyer, P.J., Van Cutsem, E., Hermann, F., Bosanac, I., Bendahmane, B., et al. (2018). MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach. J. Cancer Res. Clin. Oncol. 144, 1197–1204.10.1007/s00432-018-2632-6Suche in Google Scholar PubMed

Tian, F., Xu, J., Xue, F., Guan, E., and Xu, X. (2017). TINCR expression is associated with unfavorable prognosis in patients with hepatocellular carcinoma. Biosci. Rep. 37. PMID 28546230.10.1042/BSR20170301Suche in Google Scholar PubMed PubMed Central

Wang, J.X., Zhang, X.J., Li, Q., Wang, K., Wang, Y., Jiao, J.Q., Feng, C., Teng, S., Zhou, L.Y., Gong, Y., et al. (2015). MicroRNA-103/107 regulate programmed necrosis and myocardial ischemia/reperfusion injury through targeting FADD. Circ. Res. 117, 352–363.10.1161/CIRCRESAHA.117.305781Suche in Google Scholar PubMed

Wang, S., Ma, G., Zhu, H., Lv, C., Chu, H., Tong, N., Wu, D., Qiang, F., Gong, W., Zhao, Q., et al. (2016). miR-107 regulates tumor progression by targeting NF1 in gastric cancer. Sci. Rep. 6, 36531.10.1038/srep36531Suche in Google Scholar PubMed PubMed Central

Xu, S., Kong, D., Chen, Q., Ping, Y., and Pang, D. (2017a). Oncogenic long noncoding RNA landscape in breast cancer. Mol. Cancer 16, 129.10.1186/s12943-017-0696-6Suche in Google Scholar PubMed PubMed Central

Xu, T.P., Wang, Y.F., Xiong, W.L., Ma, P., Wang, W.Y., Chen, W.M., Huang, M.D., Xia, R., Wang, R., Zhang, E.B., et al. (2017b). E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis. Cell Death Dis. 8, e2837.10.1038/cddis.2017.205Suche in Google Scholar PubMed PubMed Central

Yang, K., Xia, B., Wang, W., Cheng, J., Yin, M., Xie, H., Li, J., Ma, L., Yang, C., Li, A., et al. (2017a). A comprehensive analysis of metabolomics and transcriptomics in cervical cancer. Sci. Rep. 7, 43353.10.1038/srep43353Suche in Google Scholar PubMed PubMed Central

Yang, X., Xiao, Z., Du, X., Huang, L., and Du, G. (2017b). Silencing of the long non-coding RNA NEAT1 suppresses glioma stem-like properties through modulation of the miR-107/CDK6 pathway. Oncol. Rep. 37, 555–562.10.3892/or.2016.5266Suche in Google Scholar PubMed

Zhang, M., Wang, X., Li, W., and Cui, Y. (2015). miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells. Biochem. Biophys. Res. Commun. 460, 806–812.10.1016/j.bbrc.2015.03.110Suche in Google Scholar PubMed

Zhang, Z.Y., Lu, Y.X., Zhang, Z.Y., Chang, Y.Y., Zheng, L., Yuan, L., Zhang, F., Hu, Y.H., Zhang, W.J., and Li, X.N. (2016). Loss of TINCR expression promotes proliferation, metastasis through activating EpCAM cleavage in colorectal cancer. Oncotarget 7, 22639–22649.10.18632/oncotarget.8141Suche in Google Scholar PubMed PubMed Central

Zhang, J., Jiang, Y., Zhu, J., Wu, T., Ma, J., Du, C., Chen, S., Li, T., Han, J., and Wang, X. (2017a). Overexpression of long non-coding RNA colon cancer-associated transcript 2 is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer. Oncol. Lett. 14, 6907–6914.10.3892/ol.2017.7049Suche in Google Scholar PubMed PubMed Central

Zhang, W., Yuan, W., Song, J., Wang, S., and Gu, X. (2017b). LncRna CPS1-IT1 suppresses cell proliferation, invasion and metastasis in colorectal cancer. Cell Physiol. Biochem. 44, 567–580.10.1159/000485091Suche in Google Scholar PubMed

Zheng, Y., Yang, C., Zheng, Y., Yang, C., Tong, S., Ding, Y., Deng, W., Song, D., and Xiao, K. (2017). Genetic variation of long non-coding RNA TINCR contribute to the susceptibility and progression of colorectal cancer. Oncotarget 8, 33536–33543.10.18632/oncotarget.16538Suche in Google Scholar PubMed PubMed Central


Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0236).


Received: 2018-04-28
Accepted: 2018-11-23
Published Online: 2019-01-06
Published in Print: 2019-05-27

©2019 Walter de Gruyter GmbH, Berlin/Boston

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