The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma.
The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma.
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包含外显子 10 的 SREK1 通过 SRSF10 的异常上调是人类肝细胞癌的致癌驱动因素
DOI：
10.1038/s41467-022-29016-x
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发表时间：
2022-03-16
影响因子：
16.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Chang C;Rajasekaran M;Qiao Y;Dong H;Wang Y;Xia H;Deivasigamani A;Wu M;Sekar K;Gao H;Sun M;Niu Y;Li Q;Tao L;Yan Z;Wang M;Chen S;Zhao S;Chen D;Li L;Yang F;Gao H;Chen B;Su L;Xu L;Chen Y;Seshachalam VP;Chen G;Gunaratne J;Hong W;Shi J;Chen G;Grierson DS;Chabot B;Xie T;Hui KM;Chen J
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 (SREK1L). SREK1L 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 SREK1L to promote hepatocarcinogenesis via the formation of a SRSF10-associated complex. In summary, we demonstrate a SRSF10/SREK1L/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.
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影响因子：
30.8
作者：
Lindeboom, Rik G. H.;Vermeulen, Michiel;Supek, Fran
通讯作者：
Supek, Fran
SRSF10介导的IL1RAP选择性剪接通过mIL1RAP-NF-kappa B-CD47轴调节宫颈癌肿瘤发生
影响因子：
8
作者：
Liu F;Dai M;Xu Q;Zhu X;Zhou Y;Jiang S;Wang Y;Ai Z;Ma L;Zhang Y;Hu L;Yang Q;Li J;Zhao S;Zhang Z;Teng Y
通讯作者：
Teng Y
starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络
影响因子：
14.9
作者：
Li JH;Liu S;Zhou H;Qu LH;Yang JH
通讯作者：
Yang JH
影响因子：
4.6
作者：
Cloutier A;Shkreta L;Toutant J;Durand M;Thibault P;Chabot B
通讯作者：
Chabot B
影响因子：
10.7
作者：
Lareau LF;Brenner SE
通讯作者：
Brenner SE