Co-targeting of EGFR by co-expressed miRNA-193a-3p/−5p in lung cancer

Abstract

Abstract MicroRNAs (miRNAs) function as important oncogenes or tumor suppressors in each stage of cancer development. While previous studies focused on the individual miRNA and its specific target gene, the cooperative functions of miRNA-3p and miRNA-5p (miRNA-3p/−5p) pairs that frequently co-exist in cells remain largely unclear. In this study, we explored the co-expression and co-targeting of the miRNA-3p/−5p pairs in lung cancer. We identified miRNA-193a-3p and miRNA-193a-5p (miRNA-193a-3p/−5p) as typical co-reduced miRNA-3p/−5p pairs in NSCLC and predicted EGFR as the co-target of miRNA-193a-3p/−5p. In agreement with this, inverse expression between miRNA-193a-3p/−5p and EGFR was detected in NSCLC tissues. Furthermore, in vitro experiments validated that miRNA-193a-3p/−5p effectively suppressed migration and proliferation in lung cancer cells. Finally, data from xenograft tumor model provided in vivo evidence for miRNA-193a-3p/−5p as tumor-suppressive miRNAs by downregulating EGFR expression. In summary, our results highlight a critical role for co-expressed miRNA-193a-3p/−5p in the co-targeting of EGFR during lung tumorigenesis.

Keywords

• Non-small cell lung cancer
• miRNA-193a-3p
• miRNA-193a-5p
• Migration
• Proliferation