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LOC554202 contributes to chordoma progression by sponging miR-377-3p and up-regulating SMAD3

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Chordoma is a rare malignant bone tumor originating from the remnants of the notochord. Here, the role of long noncoding LOC554202 in chordoma progression and its associated mechanism were explored.… Click to show full abstract

Chordoma is a rare malignant bone tumor originating from the remnants of the notochord. Here, the role of long noncoding LOC554202 in chordoma progression and its associated mechanism were explored. Cell proliferation was analyzed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide and colony formation assays. Flow cytometry was conducted to analyze cell apoptosis rate. The migration and invasion of chordoma cells were analyzed by transwell migration and invasion assays and wound healing assays. A xenograft tumor model was established in nude mice to explore the role of LOC554202 in regulating tumor growth in vivo. The interaction between microRNA-377-3p (miR-377-3p) and LOC554202 or sekelsky mothers against d PP (SMAD) family member 3 (SMAD3) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. The glycolytic rate of chordoma cells was analyzed using glucose assay kit, lactic acid kit and ApoSENSOR ADP/ATP ratio assay kit. LOC554202 expression was upregulated in chordoma tissues and cell lines. LOC554202 silencing suppressed the proliferation, migration and invasion and induced the apoptosis of chordoma cells. LOC554202 knockdown restrained xenograft tumor growth in vivo. miR-377-3p was confirmed as a target of LOC554202, and miR-377-3p silencing largely overturned LOC554202 knockdown-mediated anti-tumor effects in chordoma cells. miR-377-3p interacted with the 3′ untranslated region (3′UTR) of SMAD3 and miR-377-3p overexpression-mediated antitumor effects in chordoma cells were largely attenuated by SMAD3 overexpression. LOC554202 could positively regulate SMAD3 expression by sponging miR-377-3p in chordoma cells. LOC554202 contributed to the glycolysis of chordoma cells by targeting binding to miR-377-3p/SMAD3 axis. LOC554202 facilitated the proliferation, migration, invasion and glycolysis and inhibited the apoptosis of chordoma cells by mediating miR-377-3p/SMAD3 axis.

Keywords: chordoma; mir 377; loc554202; chordoma cells; smad3; tumor

Journal Title: Anti-Cancer Drugs
Year Published: 2022

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