The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis

Abstract

MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that are important in many biological processes. Although the oncogenic and tumour-suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumour metastasis was addressed only recently and still remains largely unexplored. To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a non-metastatic, human breast tumour cell line that was transduced with a miRNA-expression library and subjected to a trans-well migration assay. We found that human miR-373 and miR-520c stimulated cancer cell migration and invasion in vitro and in vivo, and that certain cancer cell lines depend on endogenous miR-373 activity to migrate efficiently. Mechanistically, the migration phenotype of miR-373 and miR-520c can be explained by suppression of CD44. We found significant upregulation of miR-373 in clinical breast cancer metastasis samples that correlated inversely with CD44 expression. Taken together, our findings indicate that miRNAs are involved in tumour migration and invasion, and implicate miR-373 and miR-520c as metastasis-promoting miRNAs.

Loss of p21Sdi1 expression in senescent cells after DNA damage accompanied with increase of miR-93 expression and reduced p53 interaction with p21Sdi1 gene promoter

“…Indeed, multiple microRNAs in miR-106 family and related miRNAs rescue Ras-induced senescence and induce colony formation in soft agar in HMECs via downregulation of p21 by miR-106/302 [28]. They are associated with progression of variable tumors; miR-106a and miR-106b in gastric adenocarcinoma [29], miR-17-5p and miR-372 in squamous cell carcinoma [30], miR-372 and miR-373 in testicular germ cell tumors [10], and miR-373 with miR-520c in the metastatic tumors [31]. Moreover, inactivation of p21 and p16 INK4a facilitates immortalization and anchorage independent growth of mouse fibroblasts [11].…”

Downregulation of miR-193b contributes to enhance urokinase-type plasminogen activator (uPA) expression and tumor progression and invasion in human breast cancer

“…Realtime PCR was performed using the TaqMan Gene Expression Master Mix (Applied Biosystems) and the ABI 7500 real-time There was a statistically significant Spearman's correlation that characterized an inverse relationship between miR-193b expression and uPA antigen expression (r ¼ À0.322; P ¼ 0.004). The ways of presenting the data and statistically analysing the data for every lane stem from the methods have been described earlier (Huang et al, 2008). NS, not significant.…”

“…Furthermore, miR-21 was reported to induce invasion/intravasation/metastasis in colorectal cancer (Asangani et al, 2007). miR-373 expression has been correlated with increased invasion and metastasis in breast cancer (Huang et al, 2008). miR-10b is highly expressed in metastatic breast cancer cells and positively regulates breast cancer invasion (Ma et al, 2007).…”

MicroRNA-590-5p Regulates Proliferation and Invasion in Human Hepatocellular Carcinoma Cells by Targeting TGF-β RII

“…However, a recent report showed that miR-369-3p can upregulate the expression of tumor necrosis factor alpha (Vasudevanet al, 2007). In addition, miRNAs have been shown to function as tumor suppressors or oncogenes (Bracken et al, 2009;Esquela-Kerscher et al, 2006;Huang et al, 2008;Kumar et al, 2007;Lee et al, 2007;Liu et al, 2009;Moriyama et al, 2009;Ryan et al, 2010).…”