The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma

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 () and Jianxiang Chen ()
Additional contact information
Cunjie Chang: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Muthukumar Rajasekaran: National Cancer Centre
Yiting Qiao: Zhejiang University
Heng Dong: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Yu Wang: National Cancer Centre
Hongping Xia: National Cancer Centre
Amudha Deivasigamani: National Cancer Centre
Minjie Wu: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Karthik Sekar: National Cancer Centre
Hengjun Gao: Shandong University
Mengqing Sun: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Yuqin Niu: Shihezi University
Qian Li: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Lin Tao: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Zhen Yan: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Menglan Wang: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Shasha Chen: Taizhou Cancer Hospital
Shujuan Zhao: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Dajing Chen: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Lina Li: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Fan Yang: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Haojin Gao: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Baodong Chen: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Ling Su: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Liang Xu: National University of Singapore
Ye Chen: National University of Singapore
Veerabrahma Pratap Seshachalam: National Cancer Centre
Gongxing Chen: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Jayantha Gunaratne: A*STAR, Biopolis Drive Proteos
Wanjin Hong: A*STAR, Biopolis Drive Proteos
Junping Shi: the Affiliated Hospital of Hangzhou Normal University
Gongying Chen: the Affiliated Hospital of Hangzhou Normal University
David S. Grierson: University of British Columbia
Benoit Chabot: Université de Sherbrooke
Tian Xie: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Kam Man Hui: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University
Jianxiang Chen: the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29016-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29016-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29016-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().