MicroRNA-143 suppresses oral squamous cell carcinoma cell growth, invasion and glucose metabolism through targeting hexokinase 2.
miRNAs are non-coding RNAs that have functions to regulate gene expression and play essential roles in a variety of biological processes of cancers. In the present study, we reportmiR-143acts as a tumor suppressor in human oral squamous cell carcinoma (OSCC). The expressions ofmiR-143are down-regulated in both OSCC cell lines and patient samples compared with normal adjacent tissues. We found overexpression ofmiR-143in oral cancer cell lines suppresses cell migration, cellular glucose metabolism and proliferation. Moreover, overexpression ofmiR-143promoted apoptosis and significantly caused cell cycle arrest at G1stage. The colony formation of oral cancer cells was also suppressed bymiR-143We identified hexokinase 2 (HK2) as a direct target ofmiR-143in oral cancer cells. Our data show thatmiR-143complementary pairs to the 3'-UTR of HK2 in oral cancer cells, leading to the inhibition of glycolysisin vitroandin vivoMoreover, knockdown of HK2 by siRNA in oral cancer cells inhibited glucose metabolism, proliferation and migration. Recovery of glucose metabolism by overexpression of HK2 inmiR-143overexpressing cells restores the cell migration and proliferation, suggesting that themiR-143-mediated cancer suppression is through the direct inhibition of HK2. In summary, the present studies highlightmiR-143as a tumor suppressor in OSCC by the suppression of cell migration, glucose metabolism and proliferation through directly targeting HK2, renderingmiR-143a therapeutic strategy for the treatment of clinical OSCC patients.
Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Department of Stomatology, Tianjin Third Central Hospital, Tianjin 300170, P.R. China xianghuisuntjtch@outlook.com.
Xianghui
X
Sun
Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin 300170, P.R. China.
Lei
L
Zhang
D020413:3' Untranslated Regions; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020413:3' Untranslated Regions; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C000609700:HK2 protein, human; D006593:Hexokinase; D005947:Glucose
hexokinase 2; miR-143; microRNA; oral cancer