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  • 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.

Nature communications (2022-03-18)
Cunjie Chang, Muthukumar Rajasekaran, Yiting Qiao, Heng Dong, Yu Wang, Hongping Xia, Amudha Deivasigamani, Minjie Wu, Karthik Sekar, Hengjun Gao, Mengqing Sun, Yuqin Niu, Qian Li, Lin Tao, Zhen Yan, Menglan Wang, Shasha Chen, Shujuan Zhao, Dajing Chen, Lina Li, Fan Yang, Haojin Gao, Baodong Chen, Ling Su, Liang Xu, Ye Chen, Veerabrahma Pratap Seshachalam, Gongxing Chen, Jayantha Gunaratne, Wanjin Hong, Junping Shi, Gongying Chen, David S Grierson, Benoit Chabot, Tian Xie, Kam Man Hui, Jianxiang Chen
ABSTRACT

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.

MATERIALS
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Product Description

Sigma-Aldrich
Anti-SRSF10 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
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