title: Screening and preliminary validation of miRNAs with the regulation of hTERT in colorectal cancer.
abstract: The overexpression of human telomerase reverse transcriptase (hTERT) has been associated with the invasion and metastasis of colorectal cancer (CRC) and has received extensive attention, although the underlying mechanism involved remains unclear. The aim of the present study was to screen and preliminarily validate new tumor‑suppressor microRNAs (miRNAs) that potentially inhibit hTERT expression and to assess its clinical significance. Screening for downregulated miRNAs in CRC tissues was performed by retrieving and analysing microRNA microarray data. miRNA candidates were then filtered by bioinformatics analysis. The expression of miRNAs candidates was verified by quantitative polymerase chain reaction in the CRC and corresponding normal tissues. Immunohistochemistry (IHC) was used for the detection of hTERT protein expression. Spearman's correlation coefficient between miRNA candidates and hTERT protein expression was calculated (r) to identify hTERT-targeting miRNAs. A survival analysis was performed to assess the prognostic significance of hTERT-targeting miRNAs in CRC. Eight miRNAs with the potential to interact with hTERT were predicted: miR‑29c-3p, miR‑124-3p, miR‑133a-3p, miR‑133b, miR-138-5p, miR-150-5p, miR-378a-3p and miR-422a, respectively. Following detection of the miRNAs using RT-qPCR, miR-29c-3p was excluded. miR-138-5p and miR-422a were observed to potentially interact with hTERT (r=-0.362, P=0.001; r=-0.306, P=0.005, respectively). The Kaplan-Meier survival curves demonstrating high- vs. low-expression group of miR‑422a showed a highly significant difference in CRC patients (P=0.024), which suggests that the downregulation of miR-422a was associated with a poorer prognosis. The results indicated that miR-138-5p and miR-422a potentially inhibited hTERT expression in CRC, and suggest a potential application of miR‑422a in prognosis prediction and CRC treatment.
authors.affiliation: Department of Gastrointestinal Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yu-Zhou
authors.initials: YZ
authors.lastname: Qin
authors.affiliation: Department of Gastrointestinal Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xue-Cheng
authors.initials: XC
authors.lastname: Xie
authors.affiliation: Department of Experimental Research, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Hai-Zhou
authors.initials: HZ
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lai
authors.affiliation: Department of Gastrointestinal Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Endoscopy Center, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Lian-Ying
authors.initials: LY
authors.lastname: Ge
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C546110:MIRN138 microRNA, human; C574206:MIRN422 microRNA, human; D035683:MicroRNAs; C509186:TERT protein, human; D019098:Telomerase
references.citation: Bioinformatics. 2007 Oct 15;23(20):2700-7
references.pmid: 17720982
references.citation: Science. 1995 Sep 1;269(5228):1236-41
references.pmid: 7544491
references.citation: Cytogenet Genome Res. 2008;122(3-4):263-72
references.pmid: 19188695
references.citation: Nature. 2009 Jul 23;460(7254):479-86
references.pmid: 19536157
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Int J Cancer. 2011 Aug 1;129(3):680-90
references.pmid: 20949564
references.citation: Cell Biochem Biophys. 2011 Dec;61(3):595-603
references.pmid: 21833675
references.citation: Gene. 2012 May 1;498(2):135-46
references.pmid: 22381618
references.citation: Cancer J. 2012 May-Jun;18(3):244-52
references.pmid: 22647361
references.citation: Nucleic Acids Res. 2012 Jul;40(Web Server issue):W553-9
references.pmid: 22600740
references.citation: CNS Neurosci Ther. 2012 Sep;18(9):722-8
references.pmid: 22709411
references.citation: J Cell Mol Med. 2012 Nov;16(11):2655-66
references.pmid: 22469014
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: Br J Cancer. 2013 Feb 5;108(2):278-84
references.pmid: 23322193
references.citation: Mol Med Rep. 2013 May;7(5):1409-12
references.pmid: 23525166
references.citation: Oncol Rep. 2013 May;29(5):2046-52
references.pmid: 23446431
references.citation: Int J Cancer. 2013 Aug 15;133(4):867-78
references.pmid: 23389731
references.citation: J Transl Med. 2013;11:275
references.pmid: 24171926
references.citation: Cell Death Dis. 2014;5:e1034
references.pmid: 24481448
references.citation: Methods Mol Biol. 2014;1182:289-305
references.pmid: 25055920
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: N Engl J Med. 2005 Oct 27;353(17):1768-71
references.pmid: 16251533
references.citation: Gene. 2001 May 16;269(1-2):1-12
references.pmid: 11376932
references.citation: Bioinformatics. 2001 Jun;17(6):509-19
references.pmid: 11395427
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Cancer Sci. 2008 Feb;99(2):280-6
references.pmid: 18201269