Research Paper Volume 13, Issue 10 pp 14198—14218

LncRNA LOC146880 promotes esophageal squamous cell carcinoma progression via miR-328-5p/FSCN1/MAPK axis

Jianwei Tang1, *, , Honglei Xu1, *, , Qiang Liu1, *, , Jianan Zheng1, *, , Cheng Pan1, , Zhihua Li1, , Wei Wen1, , Jun Wang1, , Quan Zhu1, , Zhibo Wang1, , Liang Chen1, ,

  • 1 Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
* Equal contribution

Received: November 11, 2020       Accepted: March 27, 2021       Published: May 18, 2021      

https://doi.org/10.18632/aging.203037
How to Cite

Copyright: © 2021 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We investigated the role of long non-coding RNA (lncRNA) LOC146880 in esophageal squamous cell carcinoma (ESCC). LOC146880 was significantly upregulated in ESCC tissues (n = 21) and cell lines compared to the corresponding controls. Higher LOC146880 expression correlated with poorer overall survival (OS) of ESCC patients. Moreover, CREB-binding protein (CBP) and H3K27 acetylation levels were significantly higher in the LOC146880 promoter in ESCC cell lines than in the controls. LOC146880 silencing inhibited in vitro proliferation, invasion, migration, and epithelial-mesenchymal transition of ESCC cells. LOC146880 silencing also induced G1-phase cell cycle arrest and apoptosis in ESCC cells. Bioinformatics analysis, dual luciferase reporter assays, and RNA immunoprecipitation assays showed that LOC146880 regulates FSCN1 expression in ESCC cells by sponging miR-328-5p. Moreover, FSCN1 expression correlated with activation of the MAPK signaling pathway in ESCC cells and tissues. In vivo xenograft tumor volume and liver metastasis were significantly reduced in nude mice injected with LOC146880-silenced ESCC cells as compared to those injected with control shRNA-transfected ESCC cells. These findings show that the LOC146880/miR-328-5p/FSCN1/MAPK axis regulates ESCC progression in vitro and in vivo. LOC146880 is thus a promising prognostic biomarker and potential therapeutic target in ESCC.

Abbreviations

lncRNAs: long noncoding RNAs; ESCC: esophageal squamous cell carcinoma; RIP: RNA immunoprecipitation; EC: esophageal cancer; miRNA: MicroRNA; EMT: Epithelial-mesenchymal transition; HEEC: human esophageal epithelial cell line; FBS: fetal bovine serum; PVDF: polyvinylidene fluoride; TBST: tris-buffered saline plus tween; HRP: horseradish peroxidase; BSA: bovine serum albumin; UTR: untranslated region; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; NaOH: sodium hydroxide; CBP: CREB-binding protein; ceRNAs: competing endogenous RNAs; miRNPs: MiRNA ribonucleoprotein complexes; ChIP-seq: chromatin immunoprecipitation sequencing; H3K27ac: acetylation of histone H3 lysine 27.