期刊
ANNALS OF TRANSLATIONAL MEDICINE
卷 8, 期 22, 页码 -出版社
AME PUBL CO
DOI: 10.21037/atm-20-7182
关键词
LMCD1 antisense RNA 1 (LMCD1-AS1); miR-1287-5p; GLI family zinc finger 2 (GLI2); thyroid cancer (THCA)
资金
- Major Special Projects of the Ministry of Science and Technology, a new strategy for accurate diagnosis and treatment of hepatitis B-related hepatocellular carcinoma with anti-recurrence and metastasis after operation [2017] [2017ZX10203207]
- National Natural Science Foundation of China, discussion on the mechanism of osteopontin interfering cholesterol metabolism and affecting cholesterol stone formation in gallbladder [2013] [81270536]
- National Natural Science Foundation of China, the role of osteopontin in the genesis of gallstones and its clinical application [2009] [30801105]
Background: LMCD1 antisense RNA 1 (LMCD1-AS1) is a certified oncogene in several tumour types. However, its role in thyroid cancer (THCA) remains unknown. Methods: The expression level of LMCD1-AS1 in THCA cells and the normal control cell was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of LMCD1-AS1 knockdown on cell proliferation, migration and apoptosis were detected by colony formation assay, EdU assay, wound healing assay and TUNEL assay. Sphere formation assay was applied to assess sphere formation ability of THCA cells. Bioinformatics analysis and mechanism experiments, including ChIP assay, RIP assay and luciferase reporter assay were conducted to evaluate the downstream and upstream molecular mechanisms of LMCD-AS1. Results: A marked up-regulation of LMCD1-AS1 in THCA cells relative to normal control cells was found. LMCD1-AS1 silencing suppressed proliferation and migration but induced apoptosis in THCA cells. Moreover, LMCD1-AS1 knockdown reduced the sphere formation capacity of THCA cells. The transcriptional factor GLI family zinc finger 2 (GLI2) binds to LMCD 1-AS 1, which contributed to LMCD 1-AS 1 up-regulation in THCA cells. Cytoplasmic LMCD 1-AS 1 sponged a shared microRNA between LMCD1-AS1 and GLI2. GLI2 was inhibited bymiR-1287-5p and disinhibited by LMCD1-AS1. Conclusions: LMCD1-AS1exerts pro-tumorigenic function through sponging miR-1287-5p to elevate GLI2 expression in THCA development, constituting a feedback loop of LMCD1-AS1/miR-1287-5p/GLI2.
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