Long Non-Coding RNA LINC01410 Promoted Tumor Progression via the ErbB Signaling Pathway by Targeting STAT5 in Gallbladder Cancer.

Lili Lu,Zhiming Wang,Weiqi Lu,Zhengqing Song,Yuhong Zhou,Shilong Zhang

doi:10.3389/fonc.2021.659123

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.

Highlights

Gallbladder cancer (GBC) is the most common biliary tract malignancy and the seventh most common gastrointestinal cancer [1]
From RNA pulldown and RNA immune-precipitation (RIP) assay, we identified that signal transducer and activator of transcription 5 (STAT5) was a critical downstream target of LINC01410
Our results suggested that LINC01410 was an important Long non-coding RNAs (lncRNAs) that promoted GBC progression via targeting STAT5 and activating ErbB signaling pathway

Summary

Introduction

Gallbladder cancer (GBC) is the most common biliary tract malignancy and the seventh most common gastrointestinal cancer [1]. Despite the encouraging developments and progress in the management of GBC, the 5-year survival of GBC patients remains less than 5% due to its highly aggressive behavior [2,3,4]. It is of much significance to screen novel and effective targets involved in GBC, which is helpful to understand the mechanism of BC tumorigenesis and progression, and to develop effective anti-tumor drugs. LncRNAs are primarily thought as since they are unable to encode proteins, and the lncRNAs have been identified as important actors in the occurrence, development, and progression of multiple malignances, including GBC. Despite the growing list of annotated lncRNAs in GBC, the experimentally verified remains small in general. The genome-wide expression patterns, biological roles of lncRNAs in GBC are yet to be elucidated

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