Heterogenous nuclear ribonucleoprotein H1 promotes colorectal cancer progression through the stabilization of mRNA of sphingosine-1- phosphate Lyase 1 （Heterogenous nuclear ribonucleoprotein H1はsphingosine-1- phosphate lyase 1 mRNAの安定化を介して大腸癌の発育を促進する）
著者
髙橋, 慶太郎
(Takahashi, Keitaro)
上位タイトル
International journal of molecular sciences
Vol.21,
No.12
(2020.
6)
,p.4514-
識別番号
ISSN
1422-0067
DOI
10.3390/ijms21124514
その他
PMID: 32630435
博士論文情報
学位授与番号
10107A552
学位授与年月日
2020-12-25
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman's rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1-SGPL1 mRNA stabilization.
