Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis

By Angie Cheng, M. Byrom, J. Shelton, L. Ford. Nucleic Acids Research, 2005

1,469 citations recorded by the source corpus.

Of the over 200 identified mammalian microRNAs (miRNAs), only a few have known biological activity. To gain a better understanding of the role that miRNAs play in specific cellular pathways, we utilized antisense molecules to inhibit miRNA activity. We used miRNA inhibitors targeting miR-23, 21, 15a, 16 and 19a to test efficacy of antisense molecules in reducing miRNA activity on reporter genes bearing miRNA-binding sites. The miRNA inhibitors de-repressed reporter gene activity when a miRNA-binding site was cloned into its 3′-untranslated region. We employed a library of miRNA inhibitors to screen for miRNA involved in cell growth and apoptosis. In HeLa cells, we found that inhibition of miR-95, 124, 125, 133, 134, 144, 150, 152, 187, 190, 191, 192, 193, 204, 211, 218, 220, 296 and 299 caused a decrease in cell growth and that inhibition of miR-21 and miR-24 had a profound increase in cell growth. On the other hand, inhibition of miR-7, 19a, 23, 24, 134, 140, 150, 192 and 193 down-regulated cell growth, and miR-107, 132, 155, 181, 191, 194, 203, 215 and 301 increased cell growth in lung carcinoma cells, A549. We also identified miRNA that when inhibited increased the level of apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased apoptosis (miR-214) in HeLa cells. From these screens, we conclude that miRNA-mediated regulation has a complexity of cellular outcomes and that miRNAs can be mediators of regulation of cell growth and apoptosis pathways.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4d5087c34ba2a3b8572b5941a7d94571a4348f93

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Citations in the corpus

Predicting miRNA‐disease association based on inductive matrix completion (2018, background): “…pointed out that miRNAs could influence multiple stages of the biological processes (Lee et al., 1993), including early cell growth, proliferation (Cheng, 2005), differentiation (Miska, 2005), development (Karp and Ambros, 2005), aging (Bartel, 2009), apoptosis, viral infection (Miska, 2005) and…”
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MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death (2008, background): “With the goal of identifying miRNAs that are relevant for proliferation or cell death, Cheng et al. (2005) individually knocked down 90 human miRNAs in HeLa and A549 cells.”
MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. (2008, neutral): “performed as previously published (31).”
MicroRNA gene expression deregulation in human breast cancer. (2005, background): “The discovery of this class of genes has identified a new layer of gene regulation mechanisms, which play an important role in development and in various cellular processes, such as differentiation, cell growth, and cell death (2).”
microRNAs as oncogenes and tumor suppressors. (2007, background): “…2000), stem cell division (Cheng et al., 2005b; Hatfield et al., 2005; Houbaviy et al., 2003; Suh et al., 2004; Zhang et al., 2006f), apoptosis (Cheng et al., 2005a; Cimmino et al., 2005; Tanno et al., 2005), disease (Abelson et al., 2005; Alvarez-Garcia and Miska, 2005), and cancer (Meltzer,…”
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Circular RNA and miR-7 in cancer. (2013, background): “Furthermore, inhibition of miR-7 caused reduced proliferation and increased apoptosis in HeLa and lung carcinoma cell lines, respectively (24), suggesting that high miR-7 expression is not necessarily beneficial in terms of inhibiting carcinogenesis.”