Abstract
miR-151a and its host gene, focal adhesion kinase, FAK, are located in a region of chromosome 8q that is frequently amplified in solid tumors, including lung cancer. Lung cancer is the leading cause of cancer deaths worldwide and metastasis remains the major challenge in battling lung cancer mortality. Here, we demonstrate that miR-151a is overexpressed in non-small cell lung cancer (NSCLC) patient specimens, as compared to healthy lung. In addition, miR-151a overexpression promotes proliferation, epithelial-to-mesenchymal transition (EMT) and induces tumor cell migration and invasion of NSCLC cells. Blocking miR-151a expression using anti-miR-151a approaches significantly reduced NCSLC cell proliferative and motility potential. Furthermore, we determined that miR-151a significantly regulates E-cadherin expression. Finally, functional rescue experiments determined that overexpression of E-cadherin in miR-151a NSCLC cell lines potently repressed miR-151a-induced partial EMT and cell migration of NSCLC cells. In conclusion, our findings suggest that miR-151a functions as an oncomiR in NSCLC by targeting E-cadherin mRNA and inducing proliferation, migration and partial EMT.
Highlights
Lung cancer has the highest mortality rate amongst human malignancies and is each year liable for 1.5 million deaths worldwide.[1]
The majority of all protein-encoding genes are subject to miR regulation and miR dysregulation has been found to be a common feature in human malignancies, including lung cancer.[13,14,15,16,17,18,19,20,21,22,23] miR-151a and its host gene, focal adhesion kinase, FAK, are located in a region of chromosome 8q that is frequently amplified in solid tumors, including lung cancer.[13,14,15,24] miR-151a is often expressed with FAK and functions synergistically, for example, by promoting metastasis in liver and prostate cancer by inhibiting RhoGDIA.[24]
We validated that miR-151a is expressed in normal lung, brain and adrenal gland tissue (Supplementary Figure S1) and performed miR-specific RT-qPCR analysis of all primary non-small cell lung cancer (NSCLC), paired distant metastases and tumor-adjacent normal lung samples. miR-151a expression levels were significantly enhanced in primary tumor as compared to normal lung tissue indicating a potential role for miR-151a during NSCLC initiation (Figure 1a, P = 0.0037)
Summary
Lung cancer has the highest mortality rate amongst human malignancies and is each year liable for 1.5 million deaths worldwide.[1]. MiR-151a expression levels were significantly enhanced in primary tumor as compared to normal lung tissue indicating a potential role for miR-151a during NSCLC initiation (Figure 1a, P = 0.0037).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
