PURPOSE: Accounting for 25% of all cancers and 20% of the cancer related-mortality, lung cancer is one of the devastating types of malignancies. The main obstacles for successful lung cancer manipulation include late diagnosis, dearth of safer chemotherapy and lack of potent therapeutic targets. Evidence indicates that microRNAs (miRs) may prove essential therapeutic targets for the management of deadly diseases, including cancer. Herein the role of miR-133 was investigated in lung cancer and the therapeutic potential of miR-133 was explored. METHODS: qRT-PCR was used for expression profiling of miR-133 and epithermal growth factor receptor (EGFR) in normal lung cell line MRC5 and lung cancer cell lines SK-MES-1, A549, A427 and DMS-53. Cell Counting Kit-8 (CCK8) assay was used to monitor the proliferation rate. Flow cytometry was used for cell cycle analysis. Apoptosis was examined by DAPI and annexin V/propidium iodide (PI) staining. TargetScan analysis was performed to identify the potential target of miR-133 and western blot analysis was done to estimate the proteins' expression. RESULTS: miR-133 was significantly (p<0.05) downregulated in lung cancer. Overexpression of miR-133 in A549 lung cancer cells caused significant (p<0.05) inhibition of their proliferation via activation of apoptotic cell death, suggestive of the tumor suppressive role of miR-133. In addition, miR-133 overexpression also resulted in significant (p<0.05) suppression of A549 cell migration and invasion. TargetScan analysis indicated EGFR to be the potential target of miR-133 in A549 cells. Analysis of EGFR expression in lung cancer cell lines showed up to 4.6 fold upregulation of EGFR. However, miR-133 overexpression resulted in downregulation of EGFR expression. Furthermore, silencing of EGFR also resulted in inhibition of proliferation, migration and invasion of A549 cells. However, overexpression of EGFR could nullify the tumor suppressive effects of miR-133, indicating EGFR inhibition is essential for the miR-133-mediated inhibitory effects on A549 cell proliferation. CONCLUSION: Taken together, miR-133 acts as a tumor suppressor and may prove essential in the management of lung cancer.
PURPOSE: Accounting for 25% of all cancers and 20% of the cancer related-mortality, lung cancer is one of the devastating types of malignancies. The main obstacles for successful lung cancer manipulation include late diagnosis, dearth of safer chemotherapy and lack of potent therapeutic targets. Evidence indicates that microRNAs (miRs) may prove essential therapeutic targets for the management of deadly diseases, including cancer. Herein the role of miR-133 was investigated in lung cancer and the therapeutic potential of miR-133 was explored. METHODS: qRT-PCR was used for expression profiling of miR-133 and epithermal growth factor receptor (EGFR) in normal lung cell line MRC5 and lung cancer cell lines SK-MES-1, A549, A427 and DMS-53. Cell Counting Kit-8 (CCK8) assay was used to monitor the proliferation rate. Flow cytometry was used for cell cycle analysis. Apoptosis was examined by DAPI and annexin V/propidium iodide (PI) staining. TargetScan analysis was performed to identify the potential target of miR-133 and western blot analysis was done to estimate the proteins' expression. RESULTS:miR-133 was significantly (p<0.05) downregulated in lung cancer. Overexpression of miR-133 in A549 lung cancer cells caused significant (p<0.05) inhibition of their proliferation via activation of apoptotic cell death, suggestive of the tumor suppressive role of miR-133. In addition, miR-133 overexpression also resulted in significant (p<0.05) suppression of A549 cell migration and invasion. TargetScan analysis indicated EGFR to be the potential target of miR-133 in A549 cells. Analysis of EGFR expression in lung cancer cell lines showed up to 4.6 fold upregulation of EGFR. However, miR-133 overexpression resulted in downregulation of EGFR expression. Furthermore, silencing of EGFR also resulted in inhibition of proliferation, migration and invasion of A549 cells. However, overexpression of EGFR could nullify the tumor suppressive effects of miR-133, indicating EGFR inhibition is essential for the miR-133-mediated inhibitory effects on A549 cell proliferation. CONCLUSION: Taken together, miR-133 acts as a tumor suppressor and may prove essential in the management of lung cancer.