BMC Cancer (Aug 2019)

Silencing of miR-182 is associated with modulation of tumorigenesis through apoptosis induction in an experimental model of colorectal cancer

  • Lisa Perilli,
  • Sofia Tessarollo,
  • Laura Albertoni,
  • Matteo Curtarello,
  • Anna Pastò,
  • Efrem Brunetti,
  • Matteo Fassan,
  • Massimo Rugge,
  • Stefano Indraccolo,
  • Alberto Amadori,
  • Stefania Bortoluzzi,
  • Paola Zanovello

DOI
https://doi.org/10.1186/s12885-019-5982-9
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 13

Abstract

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Abstract Background miR-182-5p (miR-182) is an oncogenic microRNA (miRNA) found in different tumor types and one of the most up-regulated miRNA in colorectal cancer (CRC). Although this microRNA is expressed in the early steps of tumor development, its role in driving tumorigenesis is unclear. Methods The effects of miR-182 silencing on transcriptomic profile were investigated using two CRC cell lines characterized by different in vivo biological behavior, the MICOL-14h-tert cell line (dormant upon transfer into immunodeficient hosts) and its tumorigenic variant, MICOL-14tum. Apoptosis was studied by annexin/PI staining and cleaved Caspase-3/PARP analysis. The effect of miR-182 silencing on the tumorigenic potential was addressed in a xenogeneic model of MICOL-14tum transplant. Results Endogenous miR-182 expression was higher in MICOL-14tum than in MICOL-14h-tert cells. Interestingly, miR-182 silencing had a strong impact on gene expression profile, and the positive regulation of apoptotic process was one of the most affected pathways. Accordingly, annexin/PI staining and caspase-3/PARP activation demonstrated that miR-182 treatment significantly increased apoptosis, with a prominent effect in MICOL-14tum cells. Moreover, a significant modulation of the cell cycle profile was exerted by anti-miR-182 treatment only in MICOL-14tum cells, where a significant increase in the fraction of cells in G0/G1 phases was observed. Accordingly, a significant growth reduction and a less aggressive histological aspect were observed in tumor masses generated by in vivo transfer of anti-miR-182-treated MICOL-14tum cells into immunodeficient hosts. Conclusions Altogether, these data indicate that increased miR-182 expression may promote cell proliferation, suppress the apoptotic pathway and ultimately confer aggressive traits on CRC cells.

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