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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key
Julie J Loiselle1, Justin G Roy2, Leslie C Sutherland3
1Biomolecular Sciences Program, Laurentian University, Sudbury, ON P3E 2C6, Canada.
Abstract:
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, with almost 95% of patients succumbing to the disease. Although RBM5, a tumor suppressor gene, is downregulated in the majority of lung cancers, its role in SCLC is unknown. Using the GLC20 SCLC cell line, which has a homozygous deletion encompassing the RBM5 gene locus, we established stable RBM5 expressing sublines and investigated the effects of RBM5 re-expression. Transcriptome and target identification studies determined that RBM5 directly regulates the cell cycle and apoptosis in SCLC cells, as well as significantly downregulates other important transformation-associated pathways such as angiogenesis and cell adhesion. RNA sequencing of paired non-tumor and tumor SCLC patient specimens showed decreased RBM5 expression in the tumors, and expression alterations in the majority of the same pathways that were altered in the GLC20 cells and sublines. Functional studies confirmed RBM5 expression slows SCLC cell line growth, and increases sensitivity to the chemotherapy drug cisplatin. Overall, our work demonstrates the importance of RBM5 expression to the non-transformed state of lung cells and the consequences of its deletion to SCLC development and progression.
Insights
Re-expressing the RBM5 tumor suppressor gene in small cell lung cancer (SCLC) cells slowed growth and increased chemotherapy sensitivity. This highlights RBM5
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Small cell lung cancer (SCLC) is highly aggressive with poor prognosis.
- The tumor suppressor gene RBM5 is downregulated in many cancers, but its role in SCLC is unclear.
Purpose of the Study:
- To investigate the function of RBM5 in SCLC.
- To determine the effects of RBM5 re-expression on SCLC cell lines and patient specimens.
Main Methods:
- Utilized SCLC cell line (GLC20) with RBM5 deletion to create stable RBM5-expressing sublines.
- Performed transcriptome and target identification studies.
- Conducted RNA sequencing on paired SCLC patient tumor and non-tumor samples.
- Performed functional studies on cell growth and chemosensitivity.
Main Results:
- RBM5 re-expression regulated cell cycle and apoptosis in SCLC cells.
- RBM5 significantly downregulated angiogenesis and cell adhesion pathways.
- Decreased RBM5 expression was observed in SCLC patient tumors, correlating with pathway alterations seen in cell lines.
- RBM5 expression slowed SCLC cell growth and enhanced cisplatin sensitivity.
Conclusions:
- RBM5 plays a crucial role in maintaining the non-transformed state of lung cells.
- RBM5 deletion contributes to SCLC development and progression.
- RBM5 re-expression represents a potential therapeutic strategy for SCLC.
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