title: RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways.
abstract: Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, with almost 95% of patients succumbing to the disease. AlthoughRBM5, 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 theRBM5gene locus, we established stableRBM5expressing sublines and investigated the effects ofRBM5re-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 decreasedRBM5expression in the tumors, and expression alterations in the majority of the same pathways that were altered in the GLC20 cells and sublines. Functional studies confirmedRBM5expression slows SCLC cell line growth, and increases sensitivity to the chemotherapy drug cisplatin. Overall, our work demonstrates the importance ofRBM5expression to the non-transformed state of lung cells and the consequences of its deletion to SCLC development and progression.
authors.affiliation: Biomolecular Sciences Program, Laurentian University, Sudbury, ON P3E 2C6, Canada.
authors.forename: Julie J
authors.initials: JJ
authors.lastname: Loiselle
authors.affiliation: Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON P3E 2C6, Canada.
authors.forename: Justin G
authors.initials: JG
authors.lastname: Roy
authors.affiliation: Biomolecular Sciences Program, Laurentian University, Sudbury, ON P3E 2C6, Canada; Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON P3E 2C6, Canada; Health Sciences North Research Institute (HSNRI), 41 Ramsey Lake Road, Sudbury, ON P3E 5J1, Canada.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Sutherland
keywords: Cancer research; Cell biology