Dual upregulation of miRNA-143 and miRNA-506 in non-small cell lung cancer inhibits proliferation, motility, migration, and tumor growth

Archana Shrestha¹Md Anamul Haque¹Prajesh Shrestha²Margarita Lamprou³Seetharama D. Jois²Constantinos M. Mikelis³George Mattheolabakis^1*

• ¹University of Louisiana at Monroe, Monroe, United States
• ²Louisiana State University, Baton Rouge, Louisiana, United States
• ³University of Patras, Patras, Western Greece, Greece

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide and is primarily treated with chemotherapy or radiotherapy. The role of microRNAs (miRs) is increasingly studied in cancer therapeutics, as miRs can regulate multiple cancer-related pathways simultaneously. While numerous miRs are individually explored for LC therapy, research on therapeutic miR combinations is limited. Our work here evaluates the stable deregulation of two miRs, miR-143-3p, and miR-506-3p, individually and in combination, to elucidate their roles upon prolonged exposure in non-small cell lung cancer (NSCLC) cell lines. Following stable transductions using lentiviruses in A549 and H1975 cells, we evaluated cell cycle distribution, proliferation, migration, and in vivo tumor growth. Sustained combined upregulation of miR-143-3p and miR-506-3p demonstrated a miR-expression dependent response, with advantageous responses for regulating tumor progression. The dual miR upregulation increased the G2 phase cell population and decreased cell proliferation, motility, migration, and colony formation. Furthermore, the dual upregulation significantly inhibited tumor growth in vivo compared to the respective dual downregulation, in contrast to the individual miR deregulations. Our study highlights the advantages of investigating combinatorial miRs for cancer treatment, particularly miR-143/506 against LC.