What is it about?

Colorectal cancer (CRC) is the third leading cause of cancer-related death and has an extremely poor prognosis. Dysregulation of microRNAs (miRNAs) has been shown to be involved in the pathogenesis and progression of many malignancies. Recent data suggest that microRNA-21 (miR-21) is significantly elevated in different types of cancer, especially colon adenocarcinoma. Against this background, locked nucleic acid (LNA)-modified oligonucleotides have recently been suggested as a novel approach for targeting miRNAs as antisense-based gene silencing. The aim of the current study was to explore the functional role of LNA-antimiR-21 in a colon adenocarcinoma LS174T cell line. LS174T cells were transfected with LNA-anti-miR-21 for 24, 48 and 72 h. Quantitative real-time reverse transcriptase-PCR (qRT-PCR) was performed to assess miR-21 expression by LNA-anti-miR-21. The viability of the cells was evaluated by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay and Annexin V/propidium iodide staining assay was used to detect apoptosis. Moreover, invasive behavior of the cells was evaluated before and after therapy by transwell assay. LNA-anti-miR-21 was successfully transfected in human LS174T cells and suppressed the endogenous miR-21. LNA-anti-miR-21 inhibited the cells' growth followed by induction of apoptosis. LNA-anti-miR-21 (50 pmol/μl) reduced the invasive behaviors of LS174T cells after 24 h, compared with untreated cells and scrambled LNA-transfected cells. However, this effect was more pronounced after 72 h. Our findings suggest the therapeutic potential of LNA-anti-miR-21 in a colon,adenocarcinoma for targeting miR-21 expression. Further studies are warranted to investigate the molecular mechanisms underlying this novel inhibitor in colorectal cancer to establish its potential value for treatment of CRC patients with high miR-21 expression.

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Why is it important?

we aimed to evaluate the consequences of miR-21 inhibition using LNA-modified oligonucleotides in a colon adenocarcinoma LS174T cell line.

Perspectives

Targeting miR-21 in CRC by LNA-anti-miR-21 as a potential therapeutic approach. Moreover, our data revealed that LNA-anti-miR-21 reduced cell growth, induced apoptosis and inhibited the invasiveness of LS174T colorectal adenocarcinoma cells, supporting further investigation on the role of this inhibitor in vivo model system.

Reza Nedaeinia
Student Research Committee, Department of medical biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

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This page is a summary of: Locked nucleic acid anti-miR-21 inhibits cell growth and invasive behaviors of a colorectal adenocarcinoma cell line: LNA-anti-miR as a novel approach, Cancer Gene Therapy, July 2016, Nature,
DOI: 10.1038/cgt.2016.25.
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