title: Expression and mechanisms of long non-coding RNA genes MEG3 and ANRIL in gallbladder cancer.
abstract: The objective of this study was to investigate the expression, proliferation, and apoptosis function of long-chain non-coding RNA maternally expressed gene 3 (MEG3) and antisense non-coding RNA at the INK4 locus (ANRIL) in gallbladder cancer (GBC) tissues. GBC tissues and adjacent normal samples were collected from 84 patients from January 2008 to June 2010. Empty vector, pcDNA-MEG3, and pcDNA-ANRIL vectors were transfected into GBC-SD and QBC939 cells. An MTT assay, real-time quantitative polymerase chain reaction (RT-qPCR), flow cytometry, Western blotting, and immunohistochemistry were applied. The effects of MEG3 and ANRIL were also verified in mice. Compared with normal tissues, the expression of MEG3 was significantly lower in GBC tissues, whereas the expression of ANRIL was significantly higher (both P < 0.05). The overexpression of MEG3 and underexpression of ANRIL were significantly associated with GBC prognosis (both P < 0.05). The expressions of MEG3 and ANRIL were higher in pcDNA-MEG3 and pcDNA-ANRIL-transfected cells than in empty vector-transfected cells in vitro (both P < 0.05). Most of the pcDNA-MEG3-transfected cells were in the G0-G1 phase, which showed reduced cell activity and clone counts and increased p53 and decreased cyclin D1, whereas the pcDNA-ANRIL-transfected cells were mostly in the S phase and showed contrasting behavior. Mice injected with pcDNA-MEG3-transfected cells had smaller and lighter tumors, decreased ki-67 levels, and increased caspase 3 levels, whereas those injected with pcDNA-ANRIL showed contrasting results (all P < 0.05). MEG3 can inhibit the proliferation of GBC cells and promote apoptosis, whereas ANRIL can improve the proliferation of gallbladder cells and inhibit apoptosis. Collectively, our results suggest that therapeutic strategies directed toward upregulating MEG3 and downregulating ANRIL may be clinically relevant for the inhibition of GBC deterioration.
authors.affiliation: Department of General Surgery, Xiangya No. 2 Hospital, Central South University, Renmin Road No 139, Furong Area, Changsha, 410000, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Oncology, No. 1 People's Hospital of Yueyang City, Yueyang, 414000, People's Republic of China.
authors.forename: Er-Dong
authors.initials: ED
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
authors.forename: Ming-Mei
authors.initials: MM
authors.lastname: Liao
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Hu
authors.affiliation: Department of Physiatry, Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Vascular Surgery, Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
authors.forename: Pu
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Colorectal and Anal Surgery, Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Xiangya No. 2 Hospital, Central South University, Renmin Road No 139, Furong Area, Changsha, 410000, People's Republic of China. chenweidong3115@163.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C561518:CDKN2B antisense RNA, human; C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: ANRIL; Apoptosis; Gallbladder cancer; MEG3; Proliferation
references.citation: World J Gastroenterol. 2010 Nov 21;16(43):5395-404
references.pmid: 21086555
references.citation: Natl Med J India. 2014 Jan-Feb;27(1):56
references.pmid: 25403137
references.citation: Pathol Oncol Res. 2007;13(4):326-35
references.pmid: 18158568
references.citation: J Cell Biochem. 2012 Jun;113(6):1868-74
references.pmid: 22234798
references.citation: Oncol Rep. 2014 Jul;32(1):277-85
references.pmid: 24859196
references.citation: Cell Death Dis. 2015 Jan 08;6:e1583
references.pmid: 25569100
references.citation: Mol Carcinog. 2015 Nov;54(11):1397-406
references.pmid: 25213660
references.citation: Nat Rev Cancer. 2012 Sep;12(9):613-26
references.pmid: 22898542
references.citation: J Biol Chem. 2007 Aug 24;282(34):24731-42
references.pmid: 17569660
references.citation: Ann Surg. 2006 Jun;243(6):767-71; discussion 771-4
references.pmid: 16772780
references.citation: Oncogene. 2011 Apr 21;30(16):1956-62
references.pmid: 21151178
references.citation: Trends Genet. 2006 Jan;22(1):1-5
references.pmid: 16290135
references.citation: Tumour Biol. 2011 Dec;32(6):1183-90
references.pmid: 21853312
references.citation: Hum Mol Genet. 2008 Mar 15;17(6):806-14
references.pmid: 18048406
references.citation: J Oncol. 2015;2015:967472
references.pmid: 26421012
references.citation: J Gastrointest Cancer. 2012 Jun;43(2):137-47
references.pmid: 21597894
references.citation: Oncol Rep. 2010 Sep;24(3):701-7
references.pmid: 20664976
references.citation: Cancer Epidemiol Biomarkers Prev. 2015 Sep;24(9):1319-26
references.pmid: 26070529
references.citation: Gut Liver. 2012 Apr;6(2):172-87
references.pmid: 22570746
references.citation: Int J Mol Sci. 2013 Jan 10;14(1):1278-92
references.pmid: 23306151
references.citation: Genes Cells. 2000 Mar;5(3):211-20
references.pmid: 10759892
references.citation: Appl Immunohistochem Mol Morphol. 2011 Mar;19(2):133-40
references.pmid: 21307665
references.citation: Diagn Pathol. 2015 Mar 27;10:14
references.pmid: 25889788
references.citation: FASEB J. 2011 Feb;25(2):444-8
references.pmid: 20956613
references.citation: J Exp Clin Cancer Res. 2015 Aug 08;34:79
references.pmid: 26253106
references.citation: Nat Cell Biol. 2013 Jan;15(1):2-8
references.pmid: 23263379
references.citation: PLoS One. 2012;7(11):e49462
references.pmid: 23145177
references.citation: Korean J Hepatobiliary Pancreat Surg. 2014 Nov;18(4):129-37
references.pmid: 26155265
references.citation: Cancer Res. 2010 Mar 15;70(6):2350-8
references.pmid: 20179190
references.citation: Clin Epidemiol. 2014 Mar 07;6:99-109
references.pmid: 24634588
references.citation: Trends Cell Biol. 2010 Jul;20(7):427-34
references.pmid: 20399660
references.citation: Neoplasma. 2013;60(5):486-92
references.pmid: 23790166
references.citation: J Mol Endocrinol. 2012 Apr 02;48(3):R45-53
references.pmid: 22393162
references.citation: Oncologist. 2010;15(2):168-81
references.pmid: 20147507
references.citation: Mol Biol Rep. 2012 Feb;39(2):1809-13
references.pmid: 21643759
references.citation: Biochim Biophys Acta. 2014 Nov;1842(11):2204-15
references.pmid: 25201080
references.citation: Aging Cell. 2009 Apr;8(2):152-61
references.pmid: 19239418
references.citation: Endocrinology. 2010 Jun;151(6):2443-52
references.pmid: 20392836
references.citation: Tumour Biol. 2015 Jun;36(6):4851-9
references.pmid: 25636452
references.citation: Oncotarget. 2015 Jun 10;6(16):13914-21
references.pmid: 26040010
references.citation: Mol Biosyst. 2013 Mar;9(3):407-11
references.pmid: 23295831
references.citation: Tumour Biol. 2014 Feb;35(2):1065-73
references.pmid: 24006224
references.citation: Mol Cell. 2010 Jun 11;38(5):662-74
references.pmid: 20541999
references.citation: Surgeon. 2008 Apr;6(2):101-10
references.pmid: 18488776
references.citation: Mol Cancer Ther. 2015 Jan;14(1):268-77
references.pmid: 25504755
references.citation: Stroke. 2012 Nov;43(11):2846-52
references.pmid: 22961961
references.citation: FEBS Lett. 2011 Sep 16;585(18):2803-9
references.pmid: 21624367
references.citation: Aging Cell. 2012 Jun;11(3):553-6
references.pmid: 22340434
references.citation: Int J Cancer. 2014 Nov 15;135(10):2282-93
references.pmid: 24343426