{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:43:08Z","timestamp":1786977788837,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T00:00:00Z","timestamp":1268611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor metastasis is the dominant cause of death in cancer patients, including patients with oral tongue squamous cell carcinoma (TSCC). Previously, we reported that reduced miR\u2010138 level is correlated with enhanced metastatic potential in TSCC cells. Here, we demonstrate that miR\u2010138 suppresses TSCC cell migration and invasion by regulating 2 key genes in the Rho GTPase signaling pathway: RhoC and ROCK2. Direct targeting of miR\u2010138 to specific sequences located in the 3\u2032\u2010untranslated regions of both RhoC and ROCK2 mRNAs was confirmed using luciferase reporter gene assays. Ectopic transfection of miR\u2010138 reduced the expression of both RhoC and ROCK2 in TSCC cells. These reduced expressions, in consequence, led to the reorganization of the stress fibers and the subsequent cell morphology change to a round bleb\u2010like shape as well as the suppression of cell migration and invasion. In contrast, knockdown of miR\u2010138 in TSCC cells enhanced the expression of RhoC and ROCK2, which resulted in an altered, elongated cell morphology, enhanced cell stress fiber formation and accelerated cell migration and invasion. Taken together, our results suggest that miR\u2010138 plays an important role in TSCC cell migration and invasion by concurrently targeting RhoC and ROCK2, and miR\u2010138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease.<\/jats:p>","DOI":"10.1002\/ijc.25320","type":"journal-article","created":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T11:25:02Z","timestamp":1268652302000},"page":"505-512","source":"Crossref","is-referenced-by-count":146,"title":["Downregulation of the Rho GTPase signaling pathway is involved in the microRNA\u2010138\u2010mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma"],"prefix":"10.1002","volume":"127","author":[{"given":"Lu","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Kolokythas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anxun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline 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