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

Abstract

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.

LncRNA IGFL2‐AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR‐802 in gastric cancer

“…Several lncRNAs have been documented to participate in various biological processes, especially in tumorigenesis 6–8 . Multiple lncRNAs have been reported to regulate cell proliferation, migration, invasion, and apoptosis in GC cells, such as GHET1, HOTAIR, UCA1, and CASC15 among others 9–12 . LncRNAs can act as oncogenes or tumor suppressors in GC.…”

“…[6][7][8] Multiple lncRNAs have been reported to regulate cell proliferation, migration, invasion, and apoptosis in GC cells, such as GHET1, HOTAIR, UCA1, and CASC15 among others. [9][10][11][12] LncRNAs can act as oncogenes or tumor suppressors in GC.…”

Identification of the complex regulatory relationships related to gastric cancer from lncRNA‐miRNA‐mRNA network

“…[5][6][7] In addition, studies have found that some aberrant regulations between microRNA (miRNA) and mRNA have an important impact on the progression of gastric cancer. For the abnormal regulations between long noncoding RNA (lncRNA) and messenger RNA (mRNA), some studies have shown that lncRNA can promote the proliferation and metastasis of gastric cancer cells by regulating the differentially expressed mRNA.…”

“…For the abnormal regulations between long noncoding RNA (lncRNA) and messenger RNA (mRNA), some studies have shown that lncRNA can promote the proliferation and metastasis of gastric cancer cells by regulating the differentially expressed mRNA. [5][6][7] In addition, studies have found that some aberrant regulations between microRNA (miRNA) and mRNA have an important impact on the progression of gastric cancer. 2,4,8 For the relationships of lncRNA-miRNA, although lncRNA and miRNA do not have the function of encoding proteins, the mutual regulations between lncRNA and miRNA can lead to abnormal expression of some signaling pathways and have an important influence on the growth, metastasis, metabolism, and apoptosis of gastric cancer cells.…”

WDR5 regulates epithelial-to-mesenchymal transition in breast cancer cellsviaTGFβ

“…The ability of BC cells to metastasize has been correlated with the acquisition of an EMT phenotype (Chaffer, San Juan et al, 2016). Further, previous works suggested that WDR5 might regulate metastasis formation by inducing EMT in various cancers , Malek et al, 2017, Wu, Xiang et al, 2018a. We tested whether WDR5 silencing could reduce the migratory ability of BC cells by directly inhibiting EMT.…”