The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells

被引：344

作者：

Taketo, Kosuke ^{[1
,2
,3
]}

Konno, Masamitsu ^{[2
,3
]}

Asai, Ayumu ^{[2
,3
]}

Koseki, Jun ^{[2
]}

Toratani, Masayasu ^{[1
,2
]}

Satoh, Taroh ^{[3
]}

Doki, Yuichiro ^{[4
]}

Mori, Masaki ^{[4
]}

Ishii, Hideshi ^{[2
,3
]}

Ogawa, Kazuhiko ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Radiat Oncol, Yamadaoka 2-2, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Med Data Sci, Yamadaoka 2-2, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Grad Sch Med, Dept Canc Frontier Sci, Suita, Osaka 5650871, Japan

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

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2018年 / 52卷 / 02期

关键词：

RNA methylation; METTL3; chemosensitivity; radiosensitivity; MESSENGER-RNA; NUCLEAR-RNA; DNA-REPAIR; HEAT-SHOCK; METHYLATION; N6-METHYLADENOSINE; IDENTIFICATION; MICRORNAS; UBIQUITIN; PROTEINS;

D O I：

10.3892/ijo.2017.4219

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

N-6-methyladenosine (m(6)A) is the most abundant epitranscriptome modification in mammalian mRNA. Recent years have seen substantial progress in m(6)A epitranscriptomics, indicating its crucial roles in the initiation and progression of cancer through regulation of RNA stabilities, mRNA splicing, microRNA processing and mRNA translation. However, by what means m(6)A is dynamically regulated or written by enzymatic components represented by methyltransferase-like 3 (METTL3) and how m(6)A is significant for each of the numerous genes remain unclear. We focused on METTL3 in pancreatic cancer, the prognosis of which is not satisfactory despite the development of multidisciplinary therapies. We established METTL3-knockdown pancreatic cancer cell line using short hairpin RNA. Although morphologic and proliferative changes were unaffected, METTL3-depleted cells showed higher sensitivity to anticancer reagents such as gemcitabine, 5-fluorouracil, cisplatin and irradiation. Our data suggest that METTL3 is a potent target for enhancing therapeutic efficacy in patients with pancreatic cancer. In addition, we performed cDNA expression analysis followed by gene ontology and protein-protein interaction analysis using the Database for Annotation, Visualization, and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins databases, respectively. The results demonstrate that METTL3

引用

页码：621 / 629

页数：9

共 52 条

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