Frontiers in Oncology (Jul 2021)
Long Non-Coding RNA LINC01410 Promoted Tumor Progression via the ErbB Signaling Pathway by Targeting STAT5 in Gallbladder Cancer
Abstract
ObjectivesLong non-coding RNAs (lncRNAs) have been recently emerging as crucial molecules in multiple human cancers. However, their expression patterns, roles as well as the underlying mechanisms in gallbladder cancer (GBC) remain largely unclear.Materials and MethodsThe expression of lncRNAs in GBC was downloaded from GEO database. Quantitative real-time polymerase chain reaction (qRT-PCR) and RNA in situ hybridization (ISH) were used to detect the expression of lncRNAs in GBC tissues. The full-sequence of LINC01410 was determined by RACE assay. Subcellular distribution of LINC01410 was examined by nuclear/cytoplasmic RNA fractionation analysis. Loss- and gain-of-function experiments were conducted to explore the biological functions of LINC01410 in vitro and in vivo. RNA pull-down, RNA immune-precipitation (RIP), and Western blot assay were conducted to investigate the mechanisms underlying the biological function of LINC01410 in GBC.ResultsLINC01410 was significantly upregulated in the GBC tissues compared to adjacent non-tumor tissues. High LINC01410 expression was significantly associated with poor prognosis of GBC patients. We identified LINC01410 to be 2,877 bp in length and mainly localized in the cytoplasm of GBC cells. Overexpression of LINC01410 promoted GBC cell proliferation, migration, and invasion in vitro and GBC progression in vivo, whereas LINC01410 downregulation rescued these effects in vitro. From RNA pull-down and RIP assay, we identified that STAT5 was a critical downstream target of LINC01410. Furthermore, ErbB signaling pathway was involved in the malignant phenotypes of GBC mediated by LINC01410.ConclusionsOur results suggested that LINC01410 was an important lncRNA that promoted GBC progression via targeting STAT5 and activating ErbB signaling pathway.
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