期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29016-x
关键词
-
资金
- National Natural Science Foundation of China [81802338, 82072646, 81903143, 81973635, 81730108]
- Zhejiang Provincial Natural Science Foundation of China [LR21H160001]
- Leading Goose R&D Program of Zhejiang Province [2021C03G2153004]
- Start-up Grant of HZNU [4125C5021820470]
- National Medical Research Council of Singapore
- Canadian Institutes of Health Research [MOP-136948]
- Singapore Ministry of Health's National Medical Research Council Open Fund Young Individual Research Grant [MOH-OFYIRG19Nov-0016]
In this study, the authors investigate the role of the splice variant of SREK1 and its upstream regulator SRSF10 in sustaining the oncogenic signal in hepatocarcinogenesis.
Deregulation of alternative splicing is implicated as a relevant source of molecular heterogeneity in cancer. However, the targets and intrinsic mechanisms of splicing in hepatocarcinogenesis are largely unknown. Here, we report a functional impact of a Splicing Regulatory Glutamine/Lysine-Rich Protein 1 (SREK1) variant and its regulator, Serine/arginine-rich splicing factor 10 (SRSF10). HCC patients with poor prognosis express higher levels of exon 10-inclusive SREK1 (SREK1(L)). SREK1(L) can sustain BLOC1S5-TXNDC5 (B-T) expression, a targeted gene of nonsense-mediated mRNA decay through inhibiting exon-exon junction complex binding with B-T to exert its oncogenic role. B-T plays its competing endogenous RNA role by inhibiting miR-30c-5p and miR-30e-5p, and further promoting the expression of downstream oncogenic targets SRSF10 and TXNDC5. Interestingly, SRSF10 can act as a splicing regulator for SREK1(L) to promote hepatocarcinogenesis via the formation of a SRSF10-associated complex. In summary, we demonstrate a SRSF10/SREK1(L)/B-T signalling loop to accelerate the hepatocarcinogenesis. Alternative splicing is dysregulated in hepatocellular carcinoma. Here, the authors investigate the role of the splice variant of Splicing Regulatory Glutamic Acid and Lysine Rich Protein 1 (SREK1) and its upstream regulator, Serine/arginine-rich splicing factor 10 (SRSF10) in sustaining the oncogenic signal.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据