Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma.
10.1007/s11684-024-1068-4
- Author:
Bo TIAN
1
;
Yan BIAN
1
;
Yanan PANG
1
;
Ye GAO
1
;
Chuting YU
1
;
Xun ZHANG
1
;
Siwei ZHOU
1
;
Zhaoshen LI
1
;
Lei XIN
2
,
3
;
Han LIN
4
;
Luowei WANG
3
,
5
Author Information
1. Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
2. Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. xinleiznra@
3. com.
4. Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. abyhan831@aliyun.com.
5. Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. wangluoweimd@
- Publication Type:Journal Article
- Keywords:
BOLA3;
HNRNPC;
alternative splicing;
esophageal squamous cell carcinoma;
exon skipping
- MeSH:
Female;
Humans;
Male;
Mice;
Alternative Splicing;
Cell Line, Tumor;
Disease Progression;
Esophageal Neoplasms/pathology*;
Esophageal Squamous Cell Carcinoma/pathology*;
Exons/genetics*;
Gene Expression Regulation, Neoplastic;
Heterogeneous-Nuclear Ribonucleoprotein Group C/metabolism*;
Prognosis;
RNA, Long Noncoding/metabolism*;
Animals
- From:
Frontiers of Medicine
2024;18(6):1035-1053
- CountryChina
- Language:English
-
Abstract:
Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma (ESCC) progression, but how this splicing process is abnormally regulated remains elusive. Here, we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC. The long-form BOLA3 (BOLA3-L) containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis. Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells. Additionally, HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L. High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis. HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells, which were significantly rescued by BOLA3-L overexpression. Moreover, BOLA3-L played a significant role in mitochondrial structural and functional stability. E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3. Our findings provided novel insights into how alternative splicing contributes to ESCC progression.
