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Updated: Jun 17, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
Splice-switching of the oncogenic BCS1L isoform suppresses ovarian cancer progression by disrupting mitochondrial
Meining Xu1,2, Zixiang Wang1,2, Siyuan Yang1,2
1Key Laboratory of Experimental Teratology, Ministry of Education, Department of Obstetrics and Gynecology, Qilu Hospital, Department of Cell Biology, School of Basic Medical Science, Shandong University, Jinan, China.
Abstract:
Increasing evidences demonstrate that mitochondrial function is essential for cancer cell survival and metastasis. However, the role of mitochondrial metabolic reprogramming in ovarian cancer progression remains largely unknown. Here, we report that mitochondrial chaperone BCS1L generates two major alternative-spliced isoforms, a full-length isoform (BCS1L-L) and a short isoform lacking exon 2 (BCS1L-S). Interestingly, BCS1L-L is elevated in several human cancers, and it significantly increased oxidative phosphorylation and ATP production in the present work, which is required for the survival of cancer cells. In contrast, BCS1L-S was unable to localize to the mitochondria as BCS1L-L did, and this led to impaired metabolic function. Mechanistically, splicing factor USP39 promoted exon 2 inclusion, thus facilitating the generation of oncogenic BCS1L-L and, thereby, maintaining mitochondrial homeostasis and survival of ovarian cancer cells. Importantly, we developed splice-switch antisense oligonucleotides (ASOs) that successfully induced exon 2 skipping and decreased BCS1L-L abundance, resulting in impaired tumor growth. These findings suggest that targeting oncogenic BCS1L-L by ASOs is a novel approach for ovarian cancer treatment.
Insights
Mitochondrial chaperone BCS1L promotes ovarian cancer survival through its full-length isoform (BCS1L-L). Targeting BCS1L-L with antisense oligonucleotides (ASOs) offers a novel therapeutic strategy for ovarian cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Mitochondrial function is critical for cancer cell survival and metastasis.
- The specific role of mitochondrial metabolic reprogramming in ovarian cancer progression is not well understood.
Purpose of the Study:
- To investigate the role of mitochondrial chaperone BCS1L isoforms in ovarian cancer progression.
- To explore BCS1L-L as a potential therapeutic target in ovarian cancer.
Main Methods:
- Analysis of BCS1L alternative splicing and isoform function.
- Investigated the effect of BCS1L isoforms on mitochondrial oxidative phosphorylation and ATP production.
- Developed and tested splice-switch antisense oligonucleotides (ASOs) to target BCS1L-L.
Main Results:
- BCS1L generates two isoforms: BCS1L-L (full-length) and BCS1L-S (short).
- BCS1L-L is elevated in cancers, enhances oxidative phosphorylation and ATP production, supporting cancer cell survival.
- BCS1L-S impairs mitochondrial function; splicing factor USP39 promotes oncogenic BCS1L-L generation.
- ASOs targeting BCS1L-L reduced its abundance and impaired ovarian tumor growth.
Conclusions:
- The oncogenic BCS1L-L isoform promotes ovarian cancer cell survival by enhancing mitochondrial function.
- Targeting BCS1L-L with ASOs represents a promising novel therapeutic approach for ovarian cancer treatment.
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