Association of microRNA-31 with BRAF mutation, colorectal cancer survival and serrated pathway

被引：100

作者：

Nosho, Katsuhiko ^{[1
]}

Igarashi, Hisayoshi ^{[1
]}

Nojima, Masanori ^{[2
]}

Ito, Miki ^{[1
]}

Maruyama, Reo ^{[3
]}

Yoshii, Shinji ^{[4
,5
]}

Naito, Takafumi ^{[1
]}

Sukawa, Yasutaka ^{[1
]}

Mikami, Masashi ^{[1
]}

Sumioka, Wakana ^{[1
]}

Yamamoto, Eiichiro ^{[1
]}

Kurokawa, Sei ^{[1
]}

Adachi, Yasushi ^{[1
]}

Takahashi, Hiroaki ^{[1
,4
]}

Okuda, Hiroyuki ^{[1
,4
]}

Kusumi, Takaya ^{[6
]}

Hosokawa, Masao ^{[6
]}

Fujita, Masahiro ^{[7
]}

Hasegawa, Tadashi ^{[8
]}

Okita, Kenji ^{[9
]}

Hirata, Koichi ^{[9
]}

Suzuki, Hiromu ^{[3
]}

Yamamoto, Hiroyuki ^{[10
]}

Shinomura, Yasuhisa ^{[1
]}

机构：

[1] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido 0608543, Japan

[2] Univ Tokyo, Inst Med Sci, Div Adv Med Promot, Adv Clin Res Ctr, Tokyo, Japan

[3] Sapporo Med Univ, Sch Med, Dept Mol Biol, Sapporo, Hokkaido 0608543, Japan

[4] Keiyukai Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan

[5] NTT East Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan

[6] Keiyukai Sapporo Hosp, Dept Surg, Sapporo, Hokkaido, Japan

[7] Keiyukai Sapporo Hosp, Dept Pathol, Sapporo, Hokkaido, Japan

[8] Sapporo Med Univ, Sch Med, Dept Clin Pathol, Sapporo, Hokkaido 0608543, Japan

[9] Sapporo Med Univ, Sch Med, Dept Surg Surg Oncol & Sci, Sapporo, Hokkaido 0608543, Japan

[10] St Marianna Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan

来源：

CARCINOGENESIS | 2014年 / 35卷 / 04期

基金：

日本学术振兴会;

关键词：

SQUAMOUS-CELL CARCINOMA; COLON-CANCER; MICROSATELLITE INSTABILITY; EXPRESSION PROFILES; MIR-31; ADENOCARCINOMA; PIK3CA; KRAS; IDENTIFICATION; PROLIFERATION;

D O I：

10.1093/carcin/bgt374

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

High miR-31 expression was associated with BRAF mutation and unfavourable survival in CRCs. Moreover, miR-31 inhibitor exhibited antitumour effect in colon cancer cell line, suggesting that miR-31 may be a useful biomarker and therapeutic target in CRC.BRAF is an important gene in colorectal cancers (CRCs) that is associated with molecular characterization and resistance to targeted therapy. Although microRNAs (miRNAs) are useful biomarkers of various cancers, the association between miRNA and BRAF in CRCs is undefined. Therefore, this study was conducted to identify a relationship between specific miRNA molecules and BRAF mutation in CRCs and serrated lesions. miRNA array was used for the measurement of 760 miRNAs in 29 CRCs. To assess the identified miRNAs, quantitative reverse transcriptionPCR was performed on 721 CRCs, 381 serrated lesions and 251 non-serrated adenomas. Moreover, proliferation and invasion assays were conducted using cell lines. miRNA array analysis revealed that microRNA-31 (miR-31)-5p was the most up-regulated miRNA in CRCs with mutated BRAF (V600E) compared with CRCs possessing wild-type BRAF (including cases with KRAS mutation). High miR-31 expression was associated with BRAF and KRAS mutations and proximal location (P < 0.0001). High miR-31 expression was related to cancer-specific mortality [multivariate hazard ratio 2.06, 95% confidence interval: 1.363.09, P 0.0008]. Functional analysis demonstrated that miR-31 inhibitor decreased cell invasion and proliferation. With regard to serrated lesions, high miR-31 expression was less frequently detected in hyperplastic polyps compared with other serrated lesions. In conclusion, associations were identified between miR-31, BRAF and prognosis in CRC. Transfection of miR-31 inhibitor had an antitumour effect. Thus, miR-31 may be a promising diagnostic biomarker and therapeutic target in colon cancers. Moreover, high miR-31 expression in serrated lesions suggested that miR-31 may be a key molecule in serrated pathway.

引用

页码：776 / 783

页数：8

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