GATA6-AS1 via Sponging miR-543 to Regulate PTEN/AKT Signaling Axis Suppresses Cell Proliferation and Migration in Gastric Cancer

Abstract

Gastric cancer (GC) is one of the most common and lethal cancers worldwide. In view of the prominent roles of long noncoding RNAs (lncRNAs) in cancers, we investigated the specific role and underlying mechanism of GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in GC. Quantitative real-time polymerase chain reaction (qRT-PCR) detected GATA6-AS1 expression in GC cell lines. Functional assays were conducted to explore the role of GATA6-AS1 in GC. Furthermore, mechanism investigations were implemented to uncover the interaction among GATA6-AS1, microRNA-543 (miR-543), and phosphatase and tensin homolog (PTEN). In the present study, it was found that GATA6-AS1 expression is significantly downregulated in GC cell lines. Functionally, GATA6-AS1 markedly suppresses GC cell growth and migration in vitro and in vivo tumorigenesis. Besides tumor suppressor, GATA6-AS1 serves as a miR-543 sponge. Specifically speaking, GATA6-AS1 acts as a competing endogenous RNA (ceRNA) of miR-543 to upregulate the expression of PTEN, thus inactivating AKT signaling pathway to inhibit GC progression. In conclusion, this study has manifested that GATA6-AS1 inhibits GC cell proliferation and migration as a sponge of miR-543 by regulating PTEN/AKT signaling axis, offering new perspective into developing novel GC therapies.

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

“…The top 12 genes were linked with two primary mechanisms: tumour suppressor pathway and regulation and oncogenic signalling and protein regulation: Tumour suppressor pathway and regulation: This group includes genes like PTEN, SMAD4, FBXW7 and SKP1, which are crucial for the control of cell growth, proliferation and survival. They exert a profound influence over cell cycle progression, DNA repair and the degradation of oncoproteins 43–46 Oncogenic signalling and protein regulation: This category includes genes such as MDM2, XPO1, HUWE1 and NEDD8, which are involved in oncogenic signalling and protein regulation pathways.…”

“…They exert a profound influence over cell cycle progression, DNA repair and the degradation of oncoproteins. [43][44][45][46] • Oncogenic signalling and protein regulation: This category includes genes such as MDM2, XPO1, HUWE1 and NEDD8, which are involved in oncogenic signalling and protein regulation pathways. MDM2 is a negative regulator of the tumour suppressor protein p53, while XPO1 participates in the nuclear export of various proteins.…”

Decoding the regulatory landscape of lncRNAs as potential diagnostic and prognostic biomarkers for gastric and colorectal cancers

“…In GATA6-AS1-silencedGC cells treated with LiCl, β-catenin expression is upregulated [ 243 ] HCG11 UP Wnt/ β-catenin The suppression of HCG11 inhibits the proliferation of GC cells by inhibiting the activity of the Wnt signaling pathway. The administration of LiCl the effect of HCG11 silence on the proliferation [ 244 ] LINC01133 DOWN Wnt/ β-catenin LINC01133 suppresses the nuclear accumulation of β-catenin in GC cells by sponging miR-106a-3p and promoting APC expression [ 245 ] LINC01503 UP Wnt/ β-catenin Silencing LINC01503 in GC cells reduces the expression of β-catenin, cyclin D1, and c-Myc, whereas LINC01503 upregulation reverses their expression [ 246 ] LINC01225 UP Wnt/ β-catenin LINC01225 knockdown reduces the expression ofWnt1and β-catenin in GC cells, whereas it does not affect the expression or Ser9 phosphorylation of GSK-3b [ 247 ] BANCR UP NF-kB BANCR silence decreases the expression of NFkB1 (P50/105) and inhibits the activity of NF-kB1 30 UTR [ 248 ] LINC01410 N/A NF-kB The upregulation of LINC01410 enhances the nuclear signals of NF-kBp65 and the expression of p-IKK-b, p-IkBa, and c-FLIP in GC cells, whereas LINC01410 reverses their expression [ 249 ] KRT19P3 DOWN NF-kB KRT19P3 inactivates the NF-kB signaling pathway by promoting the degradation of IkBa induced by COPS7A suppression [ ...…”