LMCD1 antisense RNA 1 (LMCD1-AS1) potentiates thyroid cancer cell growth and stemness via a positive feedback loop of LMCD1-AS1/miR-1287-5p/GLI2

Abstract

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 LMCD1-AS1, which contributed to LMCD1-AS1 up-regulation in THCA cells. Cytoplasmic LMCD1-AS1 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.