The splicing factor snrpb promotes ovarian cancer progression through regulating aberrant exon skipping of pola1 and brca2

ABSTRACT Splicing factors play a crucial role in the initiation and development of various human cancers. SNRPB, a core spliceosome component, regulates pre-mRNA alternative splicing.

However, its function and underlying mechanism in ovarian cancer remain unclear. This study identified SNRPB as a critical driver of ovarian cancer through TCGA and CPTAC database analysis.

SNRPB was highly upregulated in fresh frozen ovarian cancer tissues compared with normal fallopian tubes. Immunohistochemistry revealed that SNRPB expression was increased in formalin-fixed,

paraffin-embedded ovarian cancer sections and was positively correlated with a poor prognosis for ovarian cancer. Functionally, SNRPB knockdown suppressed ovarian cancer cell proliferation

and invasion, and overexpression exerted opposite effects. SNRPB expression increased after cisplatin treatment, and silencing SNRPB sensitized ovarian cancer cells to cisplatin. KEGG

pathway analysis revealed that the differentially expressed genes (DEGs) were mainly enriched in DNA replication and homologous recombination, and almost all DEGs related to DNA replication

and homologous recombination were downregulated after SNRPB knockdown according to RNA-seq. Exon 3 skipping of the DEGs DNA polymerase alpha 1 (POLA1) and BRCA2 was induced by SNRPB

silencing. Exon 3 skipping of POLA1 yielded premature termination codons and led to nonsense-mediated RNA decay (NMD); exon 3 skipping of BRCA2 led to loss of the PALB2 binding domain, which

is necessary for homologous recombination, and increased ovarian cancer cell cisplatin sensitivity. POLA1 or BRCA2 knockdown partially impaired the increased malignancy of

SNRPB-overexpressing ovarian cancer cells. Moreover, miR-654-5p was found to reduce SNRPB mRNA expression by directly binding to the SNRPB 3’-UTR. Overall, SNRPB was identified as an

important oncogenic driver that promotes ovarian cancer progression by repressing exon 3 skipping of POLA1 and BRCA2. Thus, SNRPB is a potential treatment target and prognostic marker for

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SF3B4 PROMOTES OVARIAN CANCER PROGRESSION BY REGULATING ALTERNATIVE SPLICING OF RAD52 Article Open access 24 February 2022

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data. Proc Natl Acad Sci USA. 2014;111:E5593–5601. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank American Journal Experts (AJE) for

English language editing. FUNDING This work was supported by National Natural Science Foundation of China (81902650, 82072871 and 82172695), the Tai-Shan Scholar Program of Shandong Province

(No. ts20070743), Shandong Province small and medium-sized scientific and technological enterprises innovation capacity improvement project (2022TSGC1347), Natural Science Foundation of

Shandong Province (ZR2021MH269), and Shenzhen Fundamental Research Program (JCYJ20220530141207017). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Obstetrics and Gynecology,

Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Ji’nan 250012, Shandong Province, China Yingwei Li, Zhongshao Chen, Jiali Peng, Cunzhong Yuan, Shi Yan, Ning Yang, Peng Li & 

Beihua Kong * Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Ji’nan 250012, Shandong Province, China Yingwei Li * Gynecology Oncology Key

Laboratory, Qilu Hospital, Shandong University, Ji’nan 250012, Shandong Province, China Yingwei Li, Zhongshao Chen, Jiali Peng, Cunzhong Yuan, Shi Yan, Ning Yang, Peng Li & Beihua Kong

Authors * Yingwei Li View author publications You can also search for this author inPubMed Google Scholar * Zhongshao Chen View author publications You can also search for this author

inPubMed Google Scholar * Jiali Peng View author publications You can also search for this author inPubMed Google Scholar * Cunzhong Yuan View author publications You can also search for

this author inPubMed Google Scholar * Shi Yan View author publications You can also search for this author inPubMed Google Scholar * Ning Yang View author publications You can also search

for this author inPubMed Google Scholar * Peng Li View author publications You can also search for this author inPubMed Google Scholar * Beihua Kong View author publications You can also

search for this author inPubMed Google Scholar CONTRIBUTIONS Conception and design: YL. Methodology: YL. Acquisition of data: YL; ZC. Analysis and interpretation of data: YL; ZC.

Administrative, technical, or material support: YL; PL; JP; ZC; SY; NY. Study supervision: YL; BK. Writing, review, and/or revision of the manuscript: YL. Final approval: All authors.

CORRESPONDING AUTHORS Correspondence to Yingwei Li or Beihua Kong. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ETHICS STATEMENT Ethical approval was

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CITE THIS ARTICLE Li, Y., Chen, Z., Peng, J. _et al._ The splicing factor SNRPB promotes ovarian cancer progression through regulating aberrant exon skipping of POLA1 and BRCA2. _Oncogene_

42, 2386–2401 (2023). https://doi.org/10.1038/s41388-023-02763-x Download citation * Received: 05 February 2023 * Revised: 08 June 2023 * Accepted: 22 June 2023 * Published: 30 June 2023 *

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