Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue

Abstract

Purpose: The aim of this study was to evaluate the microRNA expression patterns in squamous cell carcinoma (SCC) of the tongue. Experimental Design: Expression levels of 156 human mature microRNAs were examined using real-time quantitative PCR (Taq Man MicroRNA Assays; Human Panel) on laser microdissected cells of 4 tongue carcinomas and paired normal tissues. Expression of mature miR-184 was further validated in 20 paired tongue SCC and the normal tissues. Potential oncogenic functions of miR-184 were evaluated in tongue SCC cell lines (Cal27, HN21B, and HN96) with miR-184 inhibitor. Plasma miR-184 levels were evaluated using real-time quantitative PCR. Results: Using 3-fold expression difference as a cutoff level, we identified 24 up-regulated mature miRNAs including miR-184, miR-34c, miR-137, miR-372, miR-124a, miR-21, miR-124b, miR-31, miR-128a, miR-34b, miR-154, miR-197, miR-132, miR-147, miR-325, miR-181c, miR-198, miR-155, miR-30a-3p, miR-338, miR-17-5p, miR-104, miR-134, and miR-213; and 13 down-regulated mature miRNAs including miR-133a, miR-99a, miR-194, miR-133b, miR-219, miR-100, miR-125b, miR-26b, miR-138, miR-149, miR-195, miR-107, and miR-139. Overexpression of miR-184 was further validated in 20 paired tongue SCC and normal tissues (P = 0.002). Inhibition of miR-184 in tongue SCC cell lines could reduce cell proliferation rate. Down-regulation of c-Myc was observed in two cell lines in response to miR-184 inhibitor. Suppressing miR-184 could induce apoptosis in all three cell lines. Plasma miR-184 levels were significantly higher in tongue SCC patients in comparison with normal individuals, and the levels were significantly reduced after surgical removal of the primary tumors. Conclusions: Overexpression of miR-184 might play an oncogenic role in the antiapoptotic and proliferative processes of tongue SCC. In addition, plasma miR-184 levels were associated with the presence of primary tumor. Further studies on the aberrantly expressed miRNAs in tongue SCC as well as using plasma miRNAs as novel tumor markers are warranted.

MicroRNA-149 targets specificity protein 1 to suppress human tongue squamous cell carcinoma cell proliferation and motility

“…miRNA is thereby a potential diagnostic and prognostic marker of TSCC with therapeutic potential (18)(19)(20). Previous studies revealed that miR-149 was downregulated in colorectal cancer, breast cancer, gastric cancer, glioma, melanoma and non-small cell lung cancer (21)(22)(23)(24)(25)(26).…”

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].…”

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

“…One of the best described microRNAs related to cellular proliferation and apoptosis is micro-RNA-21 (hsa-miR-21). 21 hsa-miR-21 is overexpressed in many cancers, including HNSCC, 22,23 and is associated with a poor prognosis in nonsmall cell lung cancer. 24 Its targets include the tumor suppressors phosphatase and tensin homolog, 25 tropomysin 1, 26 and programmed cell death 4.…”