Abstract
This study was intended to analyze effects of lncRNA CRNDE on cervical cancer cell growth and metastasis. Fifty pairs of cervical cancer tissues and corresponding adjacent tissues were collected. Expressions of long non-coding RNAs (lncRNAs) in tissue samples were detected by microarray analysis. Expression levels of CRNDE in cervical cancer cells and normal cells were detected by qRT-PCR. Cell-counting kit-8 (CCK-8) assay and clone formation assay were utilized to evaluate cell growth. Wound healing assay and Transwell assay were conducted to detect the migratory and invasive capability of cervical cancer cells. The expressions of CRNDE in cervical cancer tissues and cells were higher than those in normal tissues and cells. CCK-8 assay and clone formation assay showed that the knockdown of CRNDE could inhibit the cell proliferation of HeLa and C-33A cells. Wound healing assay indicated that the downregulation of CRNDE expression could suppress the cell migration. The result of a Transwell assay demonstrated that the number of invasion cells reduced in the CRNDE-si group in comparison with the Mock group. LncRNA CRNDE could promote the cell growth and stimulate the metastasis of cervical cancer cells.
Ethics approval and consent to participate: All procedures of this research were in accordance with the Declaration of Helsinki and approved by the Review Ethics Committee of Harbin Medical University Cancer Hospital. All patients participated have given consent to this study.
Conflicts of interest: All authors declare that they have no conflict of interest.
References
Calore, F., Lovat, F., and Garofalo, M. (2013). Non-coding RNAs and cancer. Int. J. Mol. Sci. 14, 17085–17110.10.3390/ijms140817085Search in Google Scholar PubMed PubMed Central
Cao, S., Liu, W., Li, F., Zhao, W., and Qin, C. (2014). Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int. J. Clin. Exp. Pathol. 7, 6776–6783.Search in Google Scholar
Castellanos-Rubio, A., Fernandez-Jimenez, N., Kratchmarov, R., Luo, X., Bhagat, G., Green, P.H., Schneider, R., Kiledjian, M., Bilbao, J.R., and Ghosh, S. (2016). A long noncoding RNA associated with susceptibility to celiac disease. Science 352, 91–95.10.1126/science.aad0467Search in Google Scholar PubMed PubMed Central
Chang, Q., Chen, J., Beezhold, K.J., Castranova, V., Shi, X, and Chen, F. (2009). JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma. Mol. Cancer 8, 64.10.1186/1476-4598-8-64Search in Google Scholar PubMed PubMed Central
Chen, F.J., Sun, M., Li, S.Q., Wu, Q.Q., Ji, L., Liu, Z.L., Zhou, G.Z., Cao, G., Jin, L., Xie, H.W., et al. (2013). Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis. Mol. Carcinog. 52, 908–915.10.1002/mc.21944Search in Google Scholar PubMed
Chisholm, K.M., Wan, Y., Li, R., Montgomery, K.D., Chang, H.Y., and West, R.B. (2012). Detection of long non-coding RNA in archival tissue: correlation with polycomb protein expression in primary and metastatic breast carcinoma. PLoS One 7, e47998.10.1371/journal.pone.0047998Search in Google Scholar PubMed PubMed Central
Cifola, I., Spinelli, R., Beltrame, L., Peano, C., Fasoli, E., Ferrero, S., Bosari, S., Signorini, S., Rocco, F., Perego, R., et al. (2008). Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile. Mol. Cancer 7, 6.10.1186/1476-4598-7-6Search in Google Scholar PubMed PubMed Central
Di Gesualdo, F., Capaccioli, S., and Lulli, M. (2014). A pathophysiological view of the long non-coding RNA world. Oncotarget 5, 10976–10996.10.18632/oncotarget.2770Search in Google Scholar PubMed PubMed Central
Dong, R., Liu, X.Q., Zhang, B.B., Liu, B.H., Zheng, S., and Dong, K.R. (2017). Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma. Oncotarget 8, 42087–42097.10.18632/oncotarget.14992Search in Google Scholar PubMed PubMed Central
Ellis, B.C., Molloy, P.L., and Graham, L.D. (2012). CRNDE: a long non-coding RNA involved in cancer, neurobiology, and development. Front. Genet. 3, 270.10.3389/fgene.2012.00270Search in Google Scholar PubMed PubMed Central
Ellis, B.C., Graham, L.D., and Molloy, P.L. (2014). CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism. Biochim. Biophys. Acta 1843, 372–386.10.1016/j.bbamcr.2013.10.016Search in Google Scholar PubMed
Geng, Y.J., Xie, S.L., Li, Q., Ma, J., and Wang, G.Y. (2011). Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J. Int. Med. Res. 39, 2119–2128.10.1177/147323001103900608Search in Google Scholar PubMed
Gibb, E.A., Brown, C.J., and Lam, W.L. (2011). The functional role of long non-coding RNA in human carcinomas. Mol. Cancer 10, 38.10.1186/1476-4598-10-38Search in Google Scholar PubMed PubMed Central
Graham, L.D., Pedersen, S.K., Brown, G.S., Ho, T., Kassir, Z., Moynihan, A.T., Vizgoft, E.K., Dunne, R., Pimlott, L., Young, G.P., et al. (2011). Colorectal neoplasia differentially expressed (CRNDE), a novel gene with elevated expression in colorectal adenomas and adenocarcinomas. Genes Cancer 2, 829–840.10.1177/1947601911431081Search in Google Scholar PubMed PubMed Central
Gupta, R.A., Shah, N., Wang, K.C., Kim, J., Horlings, H.M., Wong, D.J., Tsai, M.C., Hung, T., Argani, P., Rinn, J.L., et al. (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464, 1071–1076.10.1038/nature08975Search in Google Scholar PubMed PubMed Central
Guttman, M., Amit, I., Garber, M., French, C., Lin, M.F., Feldser, D., Huarte, M., Zuk, O., Carey, B.W., Cassady, J.P., et al. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458, 223–227.10.1038/nature07672Search in Google Scholar PubMed PubMed Central
Guttman, M., Donaghey, J., Carey, B.W., Garber, M., Grenier, J.K., Munson, G., Young, G., Lucas, A.B., Ach, R., Bruhn, L., et al. (2011). lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477, 295–300.10.1038/nature10398Search in Google Scholar PubMed PubMed Central
Hu, Y., Sun, X., Mao, C., Guo, G., Ye, S., Xu, J., Zou, R., Chen, J., Wang, L., Duan, P., et al. (2017). Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration. Cancer Med. 6, 471–482.10.1002/cam4.994Search in Google Scholar PubMed PubMed Central
Huang, L., Liao, L.M., Liu, A.W., Wu, J.B., Cheng, X.L., Lin, J.X., and Zheng, M. (2014). Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer. Arch. Gynecol. Obstet. 290, 717–723.10.1007/s00404-014-3236-2Search in Google Scholar PubMed
Ishikawa, M., Yoshida, K., Yamashita, Y., Ota, J., Takada, S., Kisanuki, H., Koinuma, K., Choi, Y.L., Kaneda, R., Iwao, T., et al. (2005). Experimental trial for diagnosis of pancreatic ductal carcinoma based on gene expression profiles of pancreatic ductal cells. Cancer Sci. 96, 387–393.10.1111/j.1349-7006.2005.00064.xSearch in Google Scholar PubMed
Jiang, B., Sun, R., Fang, S., Qin, C., Pan, X., Peng, L., Li, Y., and Li, G. (2016). Lnc-CC3 increases metastasis in cervical cancer by increasing Slug expression. Oncotarget 7, 41650–41661.10.18632/oncotarget.9519Search in Google Scholar PubMed PubMed Central
Jing, L., Yuan, W., Ruofan, D., Jinjin, Y., and Haifeng, Q. (2015). HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer. Tumour Biol. 36, 3611–3619.10.1007/s13277-014-2998-2Search in Google Scholar PubMed
Khalil, A.M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B.E., van Oudenaarden, A., et al. (2009). Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc. Natl. Acad. Sci. USA 106, 11667–11672.10.1073/pnas.0904715106Search in Google Scholar PubMed PubMed Central
Kim, H.J., Lee, D.W., Yim, G.W., Nam, E.J., Kim, S., Kim, S.W., and Kim, Y.T. (2015). Long non-coding RNA HOTAIR is associated with human cervical cancer progression. Int. J. Oncol. 46, 521–530.10.3892/ijo.2014.2758Search in Google Scholar PubMed PubMed Central
Liu, X.H., Liu, Z.L., Sun, M., Liu, J., Wang, Z.X., and De, W. (2013). The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer 13, 464.10.1186/1471-2407-13-464Search in Google Scholar PubMed PubMed Central
Liu, T., Zhang, X., Yang, Y.M., Du, L.T., and Wang, C.X. (2016). Increased expression of the long noncoding RNA CRNDE-h indicates a poor prognosis in colorectal cancer, and is positively correlated with IRX5 mRNA expression. Onco Targets Ther. 9, 1437–1448.10.2147/OTT.S98268Search in Google Scholar PubMed PubMed Central
Lu, H., He, Y., Lin, L., Qi, Z., Ma, L., Li, L., and Su, Y. (2016). Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer via sponging miR-145. Tumour Biol. 37, 1683–1691.10.1007/s13277-015-3946-5Search in Google Scholar PubMed
Peng, L., Yuan, X., Jiang, B., Tang, Z., and Li, G.C. (2016). LncRNAs: key players and novel insights into cervical cancer. Tumour Biol. 37, 2779–2788.10.1007/s13277-015-4663-9Search in Google Scholar PubMed
Ponting, C.P. and Belgard, T.G. (2010). Transcribed dark matter: meaning or myth? Hum. Mol. Genet. 19, R162–168.10.1093/hmg/ddq362Search in Google Scholar PubMed PubMed Central
Ponting, C.P., Oliver, P.L., and Reik, W. (2009). Evolution and functions of long noncoding RNAs. Cell 136, 629–641.10.1016/j.cell.2009.02.006Search in Google Scholar PubMed
Rager, J.E. and Fry, R.C. (2012). The aryl hydrocarbon receptor pathway: a key component of the microRNA-mediated AML signalisome. Int. J. Environ. Res. Public Health 9, 1939–1953.10.3390/ijerph9051939Search in Google Scholar PubMed PubMed Central
Sakuragi, N. (2014). Refining insight into cervical cancer progression. Lancet Oncol. 15, 371–372.10.1016/S1470-2045(14)70085-3Search in Google Scholar
Shahab, S.W., Matyunina, L.V., Mezencev, R., Walker, L.D., Bowen, N.J., Benigno, B.B., and McDonald, J.F. (2011). Evidence for the complexity of microRNA-mediated regulation in ovarian cancer: a systems approach. PLoS One 6, e22508.10.1371/journal.pone.0022508Search in Google Scholar PubMed PubMed Central
Shang, C., Zhu, W., Liu, T., Wang, W., Huang, G., Huang, J., Zhao, P., Zhao, Y., and Yao, S. (2016). Characterization of long non-coding RNA expression profiles in lymph node metastasis of early-stage cervical cancer. Oncol Rep. 35, 3185–3197.10.3892/or.2016.4715Search in Google Scholar PubMed PubMed Central
Siegel, R.L., Miller, K.D., Fedewa, S.A., Ahnen, D.J., Meester, R.G., Barzi, A., and Jemal, A. (2017). Colorectal cancer statistics, 2017. CA Cancer J. Clin. 67, 177–193.10.3322/caac.21395Search in Google Scholar PubMed
Song, H., Han, L.M., Gao, Q., and Sun, Y. (2016). Long non-coding RNA CRNDE promotes tumor growth in medulloblastoma. Eur. Rev. Med. Pharmacol. Sci. 20, 2588–2597.Search in Google Scholar
Sun, N.X., Ye, C., Zhao, Q., Zhang, Q., Xu, C., Wang, S.B., Jin, Z.J., Sun, S.H., Wang, F., and Li, W. (2014). Long noncoding RNA-EBIC promotes tumor cell invasion by binding to EZH2 and repressing E-cadherin in cervical cancer. PLoS One 9, e100340.10.1371/journal.pone.0100340Search in Google Scholar PubMed PubMed Central
Sun, R., Qin, C., Jiang, B., Fang, S., Pan, X., Peng, L., Liu, Z., Li, W., Li, Y., and Li, G. (2016). Down-regulation of MALAT1 inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial-mesenchymal transition. Mol. Biosyst. 12, 952–962.10.1039/C5MB00685FSearch in Google Scholar
Torre, L.A., Bray, F., Siegel, R.L., Ferlay, J., Lortet-Tieulent, J., and Jemal, A. (2015). Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87–108.10.3322/caac.21262Search in Google Scholar PubMed
Wang, Y., Wang, Y., Li, J., Zhang, Y., Yin, H., and Han, B. (2015). CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling. Cancer Lett. 367, 122–128.10.1016/j.canlet.2015.03.027Search in Google Scholar PubMed
Yang, Z., Zhou, L., Wu, L.M., Lai, M.C., Xie, H.Y., Zhang, F., and Zheng, S.S. (2011). Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann. Surg. Oncol. 18, 1243–1250.10.1245/s10434-011-1581-ySearch in Google Scholar PubMed
Yang, M., Zhai, X., Xia, B., Wang, Y., and Lou, G. (2015). Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA. Tumour Biol. 36, 7615–7622.10.1007/s13277-015-3465-4Search in Google Scholar PubMed
Yang, J.P., Yang, X.J., Xiao, L., and Wang, Y. (2016). Long noncoding RNA PVT1 as a novel serum biomarker for detection of cervical cancer. Eur. Rev. Med. Pharmacol. Sci. 20, 3980–3986.Search in Google Scholar
Zhang, X., Sun, S., Pu, J.K., Tsang, A.C., Lee, D., Man, V.O., Lui, W.M., Wong, S.T., and Leung, G.K. (2012). Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol. Dis. 48, 1–8.10.1016/j.nbd.2012.06.004Search in Google Scholar PubMed
Zhang, J., Yao, T., Wang, Y., Yu, J., Liu, Y., and Lin, Z. (2016a). Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21. Cancer Biol. Ther. 17, 104–113.10.1080/15384047.2015.1108496Search in Google Scholar PubMed PubMed Central
Zhang, S., Zhang, G., and Liu, J. (2016b). Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR-200b. Acta Pathol. Microbiol. Immunol. Scand. 124, 649–658.10.1111/apm.12555Search in Google Scholar PubMed
Zhang, J., Lin, Z., Gao, Y., and Yao, T. (2017). Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer. J. Exp. Clin. Cancer Res. 36, 5.10.1186/s13046-016-0472-2Search in Google Scholar PubMed PubMed Central
Zheng, J., Liu, X., Wang, P., Xue, Y., Ma, J., Qu, C., and Liu, Y. (2016). CRNDE promotes malignant progression of glioma by attenuating miR-384/PIWIL4/STAT3 axis. Mol. Ther. 24, 1199–1215.10.1038/mt.2016.71Search in Google Scholar PubMed PubMed Central
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