Duoguang Wu1,2, Baishen Chen1,2, Fei Cui1,2, Xiaotian He1,2, Wenjian Wang1,2, Minghui Wang1,2. 1. Department of Oncology, NanfangHospital Southern Medical University, Guangzhou, China. 2. Department of Thoracic Surgery, The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.
Abstract
OBJECTIVES: Worldwide, lung cancer accounts for the majority of cancer-related deaths. Aberrant expression of miRNAs has increasingly been reported to be associated with tumour progression. This study aimed to explore the role of miR-301b in regulating apoptosis in lung cancer. MATERIALS AND METHODS: Expression of miR-301b was assessed by real-time PCR in cell lines, human patient tissues and cells treated under hypoxia and DMOG. Scramble siRNA, miR-301b inhibitor and miR-301b mimics were transfected into lung cancer cells to determine their effects on apoptosis. Additionally, a mouse xenograft model was used to explore functions of miR-301b on apoptosis, in vivo. Finally, relationships between Bim and miR-301b levels were explored by luciferase reporter assay and Western blotting. RESULTS: We found that miR-301b was highly expressed in lung cancer tissues and cell lines. Expression of miR-301b was induced by hypoxia, and miR-301b suppressed expression of Bim by targeting its 3'UTR. Functionally, ectopic expression of miR-301b enhanced cell population growth, reduced apoptosis and reduced sensitivity of cells to chemotherapy. In the xenograft model, overexpression of miR-301b promoted tumour growth. Additionally, miR-301b and Bim expression were inversely correlated in clinical lung cancer samples. CONCLUSIONS: This study provides new insights into the function of miRNA-301b in lung cancer and suggests that miRNA-301b could be a potential molecular target for chemotherapy.
OBJECTIVES: Worldwide, lung cancer accounts for the majority of cancer-related deaths. Aberrant expression of miRNAs has increasingly been reported to be associated with tumour progression. This study aimed to explore the role of miR-301b in regulating apoptosis in lung cancer. MATERIALS AND METHODS: Expression of miR-301b was assessed by real-time PCR in cell lines, humanpatient tissues and cells treated under hypoxia and DMOG. Scramble siRNA, miR-301b inhibitor and miR-301b mimics were transfected into lung cancer cells to determine their effects on apoptosis. Additionally, a mouse xenograft model was used to explore functions of miR-301b on apoptosis, in vivo. Finally, relationships between Bim and miR-301b levels were explored by luciferase reporter assay and Western blotting. RESULTS: We found that miR-301b was highly expressed in lung cancer tissues and cell lines. Expression of miR-301b was induced by hypoxia, and miR-301b suppressed expression of Bim by targeting its 3'UTR. Functionally, ectopic expression of miR-301b enhanced cell population growth, reduced apoptosis and reduced sensitivity of cells to chemotherapy. In the xenograft model, overexpression of miR-301b promoted tumour growth. Additionally, miR-301b and Bim expression were inversely correlated in clinical lung cancer samples. CONCLUSIONS: This study provides new insights into the function of miRNA-301b in lung cancer and suggests that miRNA-301b could be a potential molecular target for chemotherapy.
Authors: David E Cohn; Mateus C Barros-Filho; Brenda C Minatel; Michelle E Pewarchuk; Erin A Marshall; Emily A Vucic; Adam P Sage; Nikita Telkar; Greg L Stewart; Igor Jurisica; Patricia P Reis; Wendy P Robinson; Wan L Lam Journal: Cancers (Basel) Date: 2021-05-29 Impact factor: 6.639