Abstract
Large intergenic non-coding RNA ribonucleic acids-ROR (lincRNA-ROR) has been reported to exert impacts on the maintenance of induced pluripotent stem cells and embryonic stem cells, and play important roles in human hepatocellular cancer. It contributes to tumorigenesis and metastasis and functions as a competing endogenous RNA (ceRNA) by sponging miR-145 in breast cancer. However, its clinical significance and prognostic value in colon cancer remain unknown. The aim of the present study was to clarify the clinicopathological role and prognostic value of lincRNA-ROR and miR-145 in colon cancer. In the present study, qRT-PCR was performed to measure the expression levels of lincRNA-ROR in colon cancer tissues and cell lines. Then, the clinicopathological significance and prognostic value of lincRNA-ROR were analyzed. LincRNA-ROR expression correlated with pT stage, pN stage, AJCC stage and vascular invasion. Knockdown of lincRNA-ROR restored the expression of miR-145, and had a significant influence on colon cancer cell proliferation, migration and invasion. Patients of the high lincRNA-ROR/low miR-145 group had significantly poorer outcomes than those of the low lincRNA-ROR/high miR-145 group. Taken together, Overexpression of lincRNA-ROR combined with depletion of miR-145 may exert crucial impact on colon cancer prognosis evaluation and treatment.



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References
Brenner H, Kloor M, Pox CP (2014) Colorectal cancer. Lancet 383:1490–1502
Sieqel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA Cancer J Clin 64:104–117
Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN, et al. (2010) Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 116:544–573
Jankowski JA, Odze RD (2009) Biomarkers in gastroenterology: between hope and hype comes histopathology. Am J Gastroenterol 104:1093–1096
Modjtahedi H, Essapen S (2009) Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opporunities. Anti-Cancer Drugs 20:851–855
Aslam MI, Taylor K, Pringle JH, Jameson JS (2009) MicroRNAs are novel biomarkers of colorectal cancer. Br J Surg 96:702–710
Kiersem JB, Iksahl T, Lingjaerde OC, Guren T, Tveit KM, Kure EH (2014) Plasma microRNAs predicting clinical outcome in metastatic colorectal cancer patients receiving first-line oxaliplatin-based treatment. Mol Oncol 8:59–67
Yang F, Xue X, Bi J, Zheng L, Zhi K, Gu Y, et al. (2013) Long noncoding RNA CCAT1, which coild be activated by c-Myc, promotes the progression of gastric carcinoma. J Cancer Res Clin Oncol 139:437–445
Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, et al. (2014) P53-regulated long non- coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 5:e1243
Wu Y, Zhang L, Zhang L, Wang Y, Li H, Ren X, et al. (2015) Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by recruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. Int J Oncol 46:2586–2594
Wang L, Cai Y, Zhao X, Jia X, Zhang J, Liu J, et al. (2015) Down-regulated long non-coding RNA H19 inhibits carcinogenesis of renal cell carcinoma. Neoplasma 62:412–418
Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol 21:354–361
Khalil AM, Guttman M, Huarte M, Garber M, Rai A, Rivea Morales D, et al. (2009) Many human large intergenic noncoding RNAs associate with chromatin modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672
Guttman M, Rinn JL (2012) Modular regulatory principles of large non-coding RNAs. Nature 482:339–346
Wang Y, Xu Z, Jiang J, Xu C, Kang J, Xiao L, et al. (2013) Endogenous miRNA sponge lincRNA-ROR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25:69–80
Eades G, Wolfson B, Zhang Y, Li Q, Yao Y, Zhou Q (2015) LincRNA-ROR and miR-145 regulate invasion in triple-negative breast cancer via targeting ARF6. Mol Cancer Res 13:330–338
Zhou X, Gao Q, Wang J, Zhang X, Liu K, Duan Z (2014) Linc-RNA-ROR acts as a “spong” against mediation of the differentiation of endometrial cancer stem cells by microRNA-145. Gynecol Oncol 133:333–339
Iguchi T, Uchi R, Nambara S, Saito T, Komatsu H, Hirata H, et al. (2015) A long noncoding RNA, lncRNA-ATB, is involved in the progression and prognosis of colorectal cancer. Anticancer Res 35:1385–1388
Xu TP, Huang MD, Xia R, Liu XX, Sun M, Yin L, et al. (2014) Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression. J Hematol Oncol 7:63
Zhang ZZ, Shen ZY, Shen YY, Zhao EH, Wang M, Wang CJ, et al. (2015) HOTAIR long noncoding RNA promotes gastric cancer metastasis through suppression of poly r(c)-binding protein (PCBP) 1. Mo Cancer Ther 14:1162–1170
Wu Y, Liu H, Shi X, Yao Y, Yang W, Song Y (2015) The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma. Oncotarget 6:9160–9172
Lee H, Kim C, Ku JL, Kim W, Yoon SK, Kuh HJ, et al. (2014) A long non-coding RNA snaR contributes to 5- fluorouracil resistance in human colon cancer cells. Mol Cell 37:540–546
Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, et al. (2010) Large intergenic non-coding RNA-ROR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 42:1113–1117
Takahashi K, Yan IK, Koqure T, Haqa H, Patel T (2014) Exreacellular vesicle-mediated transfer of long non-coding RNA ROR modulates chemosensitivity in human hepatocellular cancer. FEBS Open Bio 4:458–467
Hou P, Zhao Y, Li Z, Yao R, Ma M, Gao Y, et al. (2014) LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell Death Dis 5:e1287
Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146:353–358
Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, et al. (2011) Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147:344–357
Yu CC, Tsai LL, Wang ML, Yu CH, Lo WL, Chang YC, et al. (2013) miR-145 targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6-mediated paracrine effects in head and neck cancer. Cancer Res 73:3425–3440
Noh JH, Chang YG, Kim MG, Jung KH, Kim JK, Bae HJ, et al. (2013) MiR-145 functions as a tumor suppressor by directly targeting histone deacetylase 2 in liver cancer. Cancer Lett 335:455–462
Zhang Y, Lin Q (2015) MicroRNA-145 inhibits migration and invasion by down-regulating FSCN1 in lung cancer. Int J Clin Exp Med 8:8794–8802
Qin J, Wang F, Jiang H, Xu J, Jiang Y, Wang Z (2015) MicroRNA-145 suppresses cell migration and invasion by targeting paxillin in human colorectal cancer cells. Int J Clin Exp Pathol 8:1328–1340
Foltran L, Maglio GD, Pella N, Ermacora P, Aprile G, Masiero E, et al. (2015) Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer. Future Oncol 11:629–640
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We thank Bin Zhang and Jiangming Chen for their technical assistance.
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Zhou, P., Sun, L., Liu, D. et al. Long Non-Coding RNA lincRNA-ROR Promotes the Progression of Colon Cancer and Holds Prognostic Value by Associating with miR-145. Pathol. Oncol. Res. 22, 733–740 (2016). https://doi.org/10.1007/s12253-016-0061-x
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DOI: https://doi.org/10.1007/s12253-016-0061-x