LncRNA LBX2-AS1 promotes proliferation and migratory capacity of clear cell renal cell carcinoma through mitophagy.

ABSTRACT

BACKGROUND: Long non-coding RNAs (lncRNAs) have been extensively investigated in the field of cancer, among which, lncRNA ladybird homeobox 2-antisense RNA 1 (LBX2-AS1) has been demonstrated to exert carcinogenic effects on a variety of malignancies. However, the biological functions of LBX2-AS1 in clear cell renal cell carcinoma (ccRCC) have not been explicitly elucidated. METHODS: Arraystar lncRNA chip and qRT-PCR verify the expression of LncRNA LBX2-AS1 in ccRCC. CCK-8 assay and cell cloning assay were used to assess the proliferative capacity of ccRCC cells. Migration abilities were quantified by scratch assay and transwell assay. Potential molecular signaling pathways were determined by high-throughput whole transcriptomics analysis. WB analysis was performed to validate the relationship between LBX2-AS1 and key molecules of mitophagy pathway. The effect of LBX2-AS1 on mitophagy was observed by laser confocal microscopy. Rescue experiments further validated the role of downstream gene FOXO3A in the LBX2-AS1 signaling pathway. Finally, the authentic effect of LBX2-AS1 was verified in vivo. RESULTS: LncRNA LBX2-AS1 was over expressed in ccRCC tissues and could enhance the proliferation and migration of ccRCC cells. Autophagic pathway was identified as a possible mechanism involved in the oncogenic effect of LBX2-AS1. Mitophagy levels were observed in LBX2-AS1 low-expressing cells through laser confocal microscopy. Knockdown of LBX2-AS1 significantly elevated mitophagy levels as observed using laser confocal microscopy and led to FOXOA3 decreasing in and BNIP3L and LC3 enrichment. Meanwhile, LBX2-AS1 knocking down dampened the proliferation of ccRCC cells in vivo.