SRSF1-dependent alternative splicing attenuates BIN1 expression in non-small cell lung cancer
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Updated: Jan 20, 2026
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Jiali Wang1, Tianxu Liu1, Mengjie Wang1
1Department of Tumor Immunotherapy, Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, Shijiazhuang, China.
Abstract:
Decreased bridging integrator 1 (BIN1) expression has great significance in promoting the progression of malignant tumors. Reduced messenger RNA expression is partly due to aberrant alternative splicing (AS). However, the AS status of BIN1 and its correlation with BIN1 inactivation in non-small cell lung cancer (NSCLC) remains poorly defined. Here we reported that BIN1 inactivation was not related to DNA methylation in NSCLC. Importantly, BIN1 with exon 12A inclusion (BIN1+12A isoform), the most frequent aberrant splicing variant in tumors was also observed in NSCLC, and might be accounted for BIN1 inactivation. Furthermore, we showed that the aberrant splicing of BIN1 was under the control of serine and arginine-rich factor 1 (SRSF1) in NSCLC. In addition, colony formation assay showed that BIN1+12A isoform could abolish the tumor-inhibiting ability of BIN1 in NSCLC cells. Meanwhile, transwell, wound healing and apoptosis experiments demonstrated that the occurrence of BIN1+12A could abrogate the invasion suppressing activity and proapoptotic property of BIN1 in NSCLC. Significantly, we also found that BIN1+12A isoform neutralized the tumor-suppressing functions of BIN1 via affecting its subcellular localization. Altogether, these data revealed an aberrant splicing phenomenon which abated the expression and tumor-inhibiting activity of BIN1 in NSCLC, and the related mechanisms were associated with SRSF1.
Insights
Bridging integrator 1 (BIN1) inactivation in non-small cell lung cancer (NSCLC) is linked to aberrant splicing, specifically exon 12A inclusion. This altered BIN1 isoform, regulated by SRSF1, promotes NSCLC progression by reducing tumor suppression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Decreased bridging integrator 1 (BIN1) expression is linked to malignant tumor progression.
- Aberrant alternative splicing (AS) contributes to reduced messenger RNA expression, but BIN1 AS in non-small cell lung cancer (NSCLC) is poorly understood.
- BIN1 inactivation is a key event in cancer, but its mechanisms in NSCLC require further elucidation.
Purpose of the Study:
- To investigate the alternative splicing status of BIN1 in non-small cell lung cancer (NSCLC).
- To determine the correlation between BIN1 alternative splicing and its inactivation in NSCLC.
- To elucidate the functional consequences of aberrant BIN1 splicing on tumor-suppressing activities in NSCLC.
Main Methods:
- Analysis of BIN1 alternative splicing variants in NSCLC tissues.
- Investigation of the role of serine and arginine-rich factor 1 (SRSF1) in regulating BIN1 splicing.
- Functional assays including colony formation, Transwell invasion, wound healing, and apoptosis assays.
- Assessment of BIN1 subcellular localization in NSCLC cells.
Main Results:
- BIN1 inactivation in NSCLC is not associated with DNA methylation.
- The BIN1+12A isoform, resulting from exon 12A inclusion, is a frequent aberrant splicing variant in NSCLC and may cause BIN1 inactivation.
- Aberrant BIN1 splicing in NSCLC is regulated by SRSF1.
- The BIN1+12A isoform abolishes BIN1's tumor-inhibiting ability, invasion suppression, and pro-apoptotic properties in NSCLC cells.
- BIN1+12A neutralizes BIN1's tumor-suppressing functions by altering its subcellular localization.
Conclusions:
- Aberrant splicing of BIN1, specifically exon 12A inclusion, contributes to BIN1 inactivation and loss of tumor-suppressing activity in NSCLC.
- SRSF1 plays a crucial role in regulating the aberrant splicing of BIN1 in NSCLC.
- The BIN1+12A isoform promotes NSCLC progression by abrogating BIN1's anti-tumor functions, offering potential therapeutic targets.
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