Expression of nonmuscle myosin IIC is regulated by non-canonical binding activity of miRNAs

• Published in: iScience Vol. 26; no. 12; p. 108384
• Main Authors: Banerjee, Kumarjeet, Saha, Shekhar, Das, Shaoli, Ghosal, Suman, Ghosh, Indranil, Basu, Abhimanyu, Jana, Siddhartha S.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.12.2023; Elsevier
• Subjects: Biochemistry; Cell biology; Molecular mechanism of gene regulation; Cell biology; Biochemistry; Molecular mechanism of gene regulation
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108384

The expression of mechanoresponsive nonmuscle myosin II (NMII)C is found to be inducible during tumor progression, but its mechanism is yet to be explored. Here, we report a group of microRNAs (mmu-miR-200a-5p, mmu-miR-532-3p, mmu-miR-680, and mmu-miR-1901) can significantly repress the expression of nonmuscle myosin IIC (NMIIC). Interestingly, these microRNAs have both canonical and non-canonical binding sites at 3/UTR and coding sequence (CDS) of NMIIC’s heavy chain (HC) mRNA. Each of the miRNA downregulates NMHC-IIC to a different degree as assessed by dual-luciferase and immunoblot analyses. When we abolish the complementary base pairing at canonical binding site, mmu-miR-532-3p can still bind at non-canonical binding site and form Argonaute2 (AGO2)-miRNA complex to downregulate the expression of NMIIC. Modulating the expression of NMIIC by miR-532-3p in mouse mammary tumor cells, 4T1, increases its tumorigenic potential both in vitro and in vivo. Together, these studies provide the functional role of miRNA’s non-canonical binding mediated NMIIC regulation in tumor cells. [Display omitted] •Expression of nonmuscle myosin IIC (NMIIC) can be regulated by miRNAs•Non canonical bindings of miRNAs add the efficacy of canonical bindings•Heterofilament formation of NMIIC with NMIIA and -IIB regulate cortical tension in cell Biochemistry; Molecular mechanism of gene regulation; Cell biology