MicroRNA-143 targets Syndecan-1 to repress cell growth in melanoma.
Melanoma is the most aggressive type of skin cancer with a rapid progression and a limited efficiency of therapeutics. Recently, studies have identified some microRNAs playing important roles in the development of melanoma. Syndecan-1 (Syn-1), dysregulated in many cancers, plays important roles in tumor progression by controlling cell proliferation. In this study, we investigated whether microRNA-143 (miR-143) is involved in the regulation of Syn-1 and thus plays a functional role in melanoma. We found that miR-143 expression was significantly lower in melanoma tissues than in normal tissues and its low expression was closely related to clinical stages of melanoma. Further experiments showed that consistent with the inhibitory effects induced by knockdown of Syn-1, overexpression of miR-143 suppressed cell proliferation, promoted G1 phase arrest and induced apoptosis in melanoma. Downregulation of miR-143 apparently produced opposite effects. Combined treatment of miR-143 overexpression and Syn-1 knockdown induced remarkable synergistic effects, while reconstitution of miR-143-resistant Syn-1 reversed the inhibitory activity of miR-143. Moreover, miR-143 level was inversely correlated with Syn-1 expression in melanoma cells. miR-143 directly targeted the 3'-untranslated regions of Syn-1 mRNA and they were in the same Argonaute2 complex. Taken together, this study revealed a link between miRNA-143 and Syn-1 in the pathogenesis of melanoma. MiR-143 plays an important role in the regulation of cell growth in melanoma. Restoration of miR-143 expression may represent a promising and efficient therapeutic approach for targeting malignant melanoma.
Department of Dermatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
Ruiya
R
Li
Department of Pathology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
Lingli
L
Zhang
Department of Pathology, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China.
Lizhou
L
Jia
Department of Dermatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
Yan
Y
Duan
Department of Dermatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China.
Yan
Y
Li
Department of Dermatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
Jie
J
Wang
Department of Pharmacy, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China.
Lidao
L
Bao
Department of Dermatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
Na
N
Sha
D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053668:Syndecan-1 / Q000235:genetics* / Q000378:metabolism
C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D053668:Syndecan-1