MicroRNA-205-5p suppresses the invasiveness of oral squamous cell carcinoma by inhibiting TIMP‑2 expression

Abstract

MicroRNAs (miRNAs or miRs) play important roles in carcinogenesis. The miRNA, miR-205-5p, has been reported to suppress the growth of various types of tumor; however, its functional contribution to oral squamous cell carcinoma (OSCC) is not yet clear. Thus, this study was conducted to determine the miRNA expression signatures in OSCC and to investigate the functional role of miR‑205‑5p in OSCC cells. We measured miR‑205‑5p expression by RT-qPCR, and examined the function of miR‑205‑5p by transfecting a miR‑205‑5p mimic or inhibitor into OSCC cells and measuring cell proliferation, migration and invasiveness. Genes targeted by miR‑205‑5p were identified using the TargetScan database and verified by western blot analysis, luciferase reporter assay and ELISA. We found that miR‑205‑5p was significantly downregulated in OSCC cell lines and tissue specimens. Following transfection of miR‑205‑5p mimic or inhibitor into the cancer cell lines, miR‑205‑5p overexpression significantly suppressed cancer cell migration and invasion. We further demonstrated that miR‑205‑5p directly targeted and regulated the tissue inhibitor of metalloproteinases‑2 (TIMP‑2) gene. The silencing of TIMP‑2 suppressed cancer cell invasion and the activation of pro‑matrix metalloproteinase‑2 (pro‑MMP‑2). These results suggest that TIMP‑2 promotes tumor progression, and that miR‑205‑5p directly regulates TIMP‑2, thereby suppressing pro‑MMP‑2 activation and inhibiting OSCC cell invasiveness. Our data describing the pathways regulated by miR‑205‑5p provide new insight into the mechanisms responsible for OSCC development and metastasis.

Long non-coding RNA SNHG5 promotes glioma progression via miR-205/E2F3 axis

“…MiR-205 functions as a tumour suppressor in human cancers, such as breast cancer, prostatic carcinoma and oral squamous cell carcinoma [27][28][29]. Our study found that miR-205 suppressed the glucose uptake, migration and invasion of glioma cells.…”

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

“…Oral squamous cell carcinoma (OSCC) represents over 90% of oral cavity cancers [1,2], with a rapidly increasing incidence among young and middle-aged individuals due to excessive smoking and alcohol consumption [3]. Despite efforts to improve its early diagnosis and treatment, advanced OSCC still has an extremely poor 5-year survival rate of less than 63%, mainly due to high recurrence rates brought about by its ability to invade local tissues and to metastasize [4].…”

Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma—A Review

“…In OSCC, tumor suppressive miRNAs are frequently downregulated. In OSCC, many tumor suppressive miRNAs are involved in invasion, as the following; miR-222 (via targeting MMP1 and manganese superoxide dismutase 2: SOD2), miR-138, miR-363 (via targeting podoplanin), miR-491-5p (via targeting G-protein-coupled receptor kinase-interacting protein 1: GIT1), miR-140-5p, miR-133b, miR-29b (via targeting Sp1), miR-125a (via targeting estrogen-related receptor α: ESRRA), miR-34a (via targeting MMP9 and MMP14), miR-329 and miR-410 (via targeting Wnt-7b), miR-143 (via targeting CD44 v3), miR-222 (via targeting ATP-binding cassette sub-family G member 2: ABCG2), miR-188 (via targeting SIX1), miR-196b, miR-23b and miR-27b (via targeting receptor tyrosine kinase MET), miR-200c-3p (via targeting chromodomain-helicase-DNA-binding protein 9: CHD9 and Werner syndrome ATP-dependent helicase, WRN), miR-205-p (via targeting the tissue inhibitor of metalloproteinases‑2: TIMP‑2), miR-22 (via targeting NLR family pyrin domain containing three: NLRP3), miR-195-5p (via targeting tripartite motif-containing protein: TRIM14), miR-30a-5p (via targeting fibroblast activation protein α: FAP), miR-376c-3p (via targeting HOXB7), miR-143 (via targeting hexokinase 2), miR‑375 (via targeting platelet‑derived growth factor‑A: PDGF-A), and miR-320a suppress the invasion as a tumor suppressive miRNA [ 114 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 145 ].…”