MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer

被引：139

作者：

Hasegawa, S. ^{[1
,2
]}

Eguchi, H. ^{[1
]}

Nagano, H. ^{[1
]}

Konno, M. ^{[2
]}

Tomimaru, Y. ^{[1
]}

Wada, H. ^{[1
]}

Hama, N. ^{[1
]}

Kawamoto, K. ^{[1
]}

Kobayashi, S.

Nishida, N. ^{[2
]}

Koseki, J. ^{[3
]}

Nishimura, T. ^{[4
]}

Gotoh, N. ^{[4
]}

Ohno, S. ^{[5
]}

Yabuta, N. ^{[5
]}

Nojima, H. ^{[5
]}

Mori, M. ^{[1
]}

Doki, Y. ^{[1
]}

Ishii, H. ^{[2
,3
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Surg Gastroenterol, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Frontier Sci Canc & Chemotherapy, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Grad Sch Med, Dept Canc Profiling Discovery, Suita, Osaka 5650871, Japan

[4] Univ Tokyo, Inst Med Sci, Div Mol Therapy, Mol Targets Lab,Minato Ku, Tokyo 1088639, Japan

[5] Osaka Univ, Microbial Dis Res Inst, Dept Mol Genet, Suita, Osaka 5650871, Japan

来源：

BRITISH JOURNAL OF CANCER | 2014年 / 111卷 / 08期

关键词：

microRNA; miR-1246; CCNG2; chemoresistance; cancer stem cell; pancreatic cancer; CYCLIN G2; MALIGNANT-TRANSFORMATION; DECREASED EXPRESSION; CELLS; GEMCITABINE; DYSREGULATION; SENSITIVITY; RESISTANCE; CARCINOMA; MIR-200;

D O I：

10.1038/bjc.2014.454

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background: Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance. Methods: We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. Results: The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. Conclusions: miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.

引用

页码：1572 / 1580

页数：9

共 27 条

[1]

RETRACTED: Gemcitabine Sensitivity Can Be Induced in Pancreatic Cancer Cells through Modulation of miR-200 and miR-21 Expression by Curcumin or Its Analogue CDF (Retracted article. See vol. 78, pg. 5466, 2018) [J].