Testis-specific hnRNP is expressed in colorectal cancer cells and accelerates cell growth mediating ZDHHC11 mRNA stabilization （精巣特異的hnRNPは大腸癌で過剰発現しZDHHC11 mRNAの安定化を介して腫瘍増殖を促進する）
著者
村上, 雄紀
(Murakami, Yuki)
上位タイトル
Cancer medicine
識別番号
ISSN
2045-7634
DOI
10.1002/cam4.4738
その他
PMID:35384384
博士論文情報
学位授与番号
10107A579
学位授与年月日
2022-06-30
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
Various heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be associated with cancer cell growth. However, it remains unclear whether hnRNP G-T, which is specifically expressed in the testis, is expressed in tumor cells, and whether hnRNP G-T expressed in colorectal cancer (CRC) cells is associated with tumor progression. We herein report that hnRNP G-T promoted cancer cell growth and stabilized mRNA of ZDHHC11 in CRC. The cell growth was inhibited by transfection of siRNA of hnRNP G-T in cancer cells, but not in non-cancerous epithelial cells. The tumor promotive effect of hnRNP G-T was confirmed in an HCT116 transplanted mouse model. RT-PCR and western blotting indicated the augmentation of hnRNP G-T in CRC in comparison to non-cancerous cells. The downregulation of hnRNP G-T inhibited cancer cell growth and promoted apoptosis in CRC. A transcriptome analysis combined with immunoprecipitation revealed that hnRNP G-T stabilized 174 mRNAs, including ZDHHC11 mRNA. The cell growth was also suppressed by the transfection of siRNA of ZDHHC11 and the mRNA and the protein expression were decreased by the transfection of siRNA of hnRNP G-T. These results suggested that hnRNP G-T promotes the cell growth of CRC by regulating the mRNA of ZDHHC11. Therefore, hnRNP G-T will be highlighted as an effective therapeutic target with less adverse effects in CRC therapy
