Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1

Long non‐coding RNA (lncRNA) is responsible for a diverse range of cellular functions, such as transcriptional and translational regulation and variance in gene expression. The lncRNA CASC15 (cancer susceptibility candidate 15) is a long intergenic non‐coding RNA (lincRNA) locus in chromosome 6p22.3...

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Main Authors: Qiong Wu, Shihao Xiang, Jiali Ma, Pingping Hui, Ting Wang, Wenying Meng, Min Shi, Yugang Wang
Format: Article
Language:English
Published: Wiley 2018-06-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.12187
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spelling doaj-fda1085b44f548f9a3023dec390be1c42020-11-25T02:54:04ZengWileyMolecular Oncology1574-78911878-02612018-06-0112679981310.1002/1878-0261.12187Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1Qiong Wu0Shihao Xiang1Jiali Ma2Pingping Hui3Ting Wang4Wenying Meng5Min Shi6Yugang Wang7Department of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaDepartment of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaDepartment of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaDepartment of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaDepartment of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaDepartment of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaDepartment of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaDepartment of Gastroenterology Tongren Hospital Shanghai Jiao Tong University School of Medicine ChinaLong non‐coding RNA (lncRNA) is responsible for a diverse range of cellular functions, such as transcriptional and translational regulation and variance in gene expression. The lncRNA CASC15 (cancer susceptibility candidate 15) is a long intergenic non‐coding RNA (lincRNA) locus in chromosome 6p22.3. Previous research shows that lncRNA CASC15 is implicated in the biological behaviors of several cancers such as neuroblastoma and melanoma. Here, we aimed to explore in detail how CASC15 contributes to the growth of gastric cancer (GC). As predicted, the expression of CASC15 was enriched in GC tissues and cell lines as compared with healthy tissues and cells using qRT‐PCR. The Kaplan–Meier method was used to demonstrate that high expression of CASC15 is linked to a poor prognosis for patients suffering from GC. Additionally, functional experiments proved that the down‐ or up‐regulation of CASC15 inhibited or facilitated cell proliferation via the induction of cell cycle arrest and apoptosis, and also suppressed or accelerated cell migration and invasion by affecting the progression of the epithelial‐to‐mesenchymal transition (EMT). In vivo experiments showed that the knockdown of CASC15 lessened the tumor volume and weight and influenced the EMT process. This was confirmed by western blot assays and immunohistochemistry, indicating impaired metastatic ability in nude mice. CASC15 involvement in the tumorigenesis of GC occurs when CASC15 interacts with EZH2 and WDR5 to modulate CDKN1A in nucleus. Additionally, the knockdown of CASC15 triggered the silencing of ZEB1 in cytoplasm, which was shown to be associated with the competitive binding of CASC15 to miR‐33a‐5p.https://doi.org/10.1002/1878-0261.12187cancer susceptibility candidate 15CDKN1Aepithelial‐to‐mesenchymal transitiongastric cancerZEB1
collection DOAJ
language English
format Article
sources DOAJ
author Qiong Wu
Shihao Xiang
Jiali Ma
Pingping Hui
Ting Wang
Wenying Meng
Min Shi
Yugang Wang
spellingShingle Qiong Wu
Shihao Xiang
Jiali Ma
Pingping Hui
Ting Wang
Wenying Meng
Min Shi
Yugang Wang
Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1
Molecular Oncology
cancer susceptibility candidate 15
CDKN1A
epithelial‐to‐mesenchymal transition
gastric cancer
ZEB1
author_facet Qiong Wu
Shihao Xiang
Jiali Ma
Pingping Hui
Ting Wang
Wenying Meng
Min Shi
Yugang Wang
author_sort Qiong Wu
title Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1
title_short Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1
title_full Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1
title_fullStr Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1
title_full_unstemmed Long non‐coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1
title_sort long non‐coding rna casc15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting cdkn1a and zeb1
publisher Wiley
series Molecular Oncology
issn 1574-7891
1878-0261
publishDate 2018-06-01
description Long non‐coding RNA (lncRNA) is responsible for a diverse range of cellular functions, such as transcriptional and translational regulation and variance in gene expression. The lncRNA CASC15 (cancer susceptibility candidate 15) is a long intergenic non‐coding RNA (lincRNA) locus in chromosome 6p22.3. Previous research shows that lncRNA CASC15 is implicated in the biological behaviors of several cancers such as neuroblastoma and melanoma. Here, we aimed to explore in detail how CASC15 contributes to the growth of gastric cancer (GC). As predicted, the expression of CASC15 was enriched in GC tissues and cell lines as compared with healthy tissues and cells using qRT‐PCR. The Kaplan–Meier method was used to demonstrate that high expression of CASC15 is linked to a poor prognosis for patients suffering from GC. Additionally, functional experiments proved that the down‐ or up‐regulation of CASC15 inhibited or facilitated cell proliferation via the induction of cell cycle arrest and apoptosis, and also suppressed or accelerated cell migration and invasion by affecting the progression of the epithelial‐to‐mesenchymal transition (EMT). In vivo experiments showed that the knockdown of CASC15 lessened the tumor volume and weight and influenced the EMT process. This was confirmed by western blot assays and immunohistochemistry, indicating impaired metastatic ability in nude mice. CASC15 involvement in the tumorigenesis of GC occurs when CASC15 interacts with EZH2 and WDR5 to modulate CDKN1A in nucleus. Additionally, the knockdown of CASC15 triggered the silencing of ZEB1 in cytoplasm, which was shown to be associated with the competitive binding of CASC15 to miR‐33a‐5p.
topic cancer susceptibility candidate 15
CDKN1A
epithelial‐to‐mesenchymal transition
gastric cancer
ZEB1
url https://doi.org/10.1002/1878-0261.12187
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