LINC00355 promotes gastric carcinogenesis by scaffolding p300 to activate CDC42 transcription and enhancing HNRNPA2B1 to stabilize CDC42 mRNA dependent on m6A

被引：2

作者：

Chen, Hui ^{[1
]}

Xiao, Lanshu ^{[1
,2
]}

Xie, Guohua ^{[1
]}

Zhang, Peng ^{[1
]}

Dong, Ping ^{[3
]}

Bian, Bingxian ^{[1
]}

Wang, Jie ^{[4
]}

Zhou, Yunlan ^{[1
]}

Ma, Yanhui ^{[1
]}

Liu, Yi ^{[1
,7
]}

Shen, Lisong ^{[1
,5
,6
,7
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Clin Lab, Shanghai, Peoples R China

[2] Chongqing Univ Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis & I, Chongqing, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gen Surg, Shanghai, Peoples R China

[4] Shanghai Ruijin Rehabil Hosp, Dept Clin Lab, Shanghai, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Med, Coll Hlth Sci & Technol, Fac Med Lab Sci, Shanghai, Peoples R China

[6] Shanghai Acad Expt Med, Inst Artificial Intelligence Med, Shanghai, Peoples R China

[7] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Clin Lab, Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

来源：

MOLECULAR CARCINOGENESIS | 2024年 / 63卷 / 03期

基金：

中国国家自然科学基金;

关键词：

CDC42; gastric carcinogenesis; LINC00355; p300; NONCODING RNAS; CELL-PROLIFERATION; MODULAR SCAFFOLD; CANCER; INVASION; LNCRNA; PROGRESSION; EXPRESSION; COMPLEXES; RAC1;

D O I：

10.1002/mc.23662

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

LINC00355 is involved in the tumorigenesis of several types of cancer. We verified that LINC00355 is upregulated in gastric cancer (GC) and contributes to GC cells' proliferation and metastasis. RNA sequencing (RNA-seq) and rescue assays suggested that LINC00355 controls gastric carcinogenesis by regulating the expression of cell division cycle 42 (CDC42) guanosine triphosphatase (GTPases), thereby activating their downstream pathways. Most previous studies have shown that LINC00355 acts as a ceRNA by sponging miRNAs to modulate downstream gene expression. Our group focus on epigenetic regulatory potential of LINC00355 in gene expression. Mechanistically, LINC00355 binds to p300 histone acetyltransferase, specifying the histone modification pattern on the CDC42 promoter to activate CDC42 transcription, thereby altering GC cell biology. In addition, HNRNPA2B1, which is upregulated by LINC00355, recognizes the N6-methyladenosine (m6A) sites of CDC42 and enhances the stability of CDC42 mRNA transcripts. Therefore, LINC00355 is mechanistically, functionally, and clinically oncogenic in GC cells.

引用

页码：430 / 447

页数：18