<p>microRNA-582 Potentiates Liver and Lung Metastasis of Gastric Carcinoma Cells Through the FOXO3-Mediated PI3K/Akt/Snail Pathway</p>

Abstract

Background: The dysregulation of microRNA (miRNAs) is broadly participated in cancer progression, resulting in sustained cell proliferation by directly targeting various targets. This study investigated the expression of miR-582 in GC and its association with liver metastasis. Methods: Firstly, differentially expressed miRNAs in gastric cancer (GC) tissues were predicted by microarray. Then, the relationship between miR-582 and clinical characteristics of GC patients was analyzed. By silencing of miR-582 in GC cells, the change in malignant biological behaviors of GC cells was detected. The upstream lncRNA, downstream targeting genes of miR-582 and the corresponding signaling pathway were predicted by online databases and verified by luciferase reporter assays, RT-qPCR and Western blot analysis. Finally, the effects of miR-582 on the growth and metastasis of GC cells were detected by in vivo tumorigenesis and metastasis tests. Results: MiR-582 was highly expressed in GC tissues and related to the metastasis of patients with GC. Silencing of miR-582 expression blocked malignant biological behaviors of GC cells in vitro and in vivo. MiR-582 inhibited forkhead box protein O3 (FOXO3) to upregulate the PI3K/AKT/Snail signaling pathway in GC cells. Besides, GATA6-AS1 was found as an upstream lncRNA to modulate the expression of miR-582. Conclusion: MiR-582 induced by GATA6-AS1 silencing promotes the growth and metastasis of GC cells by targeting FOXO3 to induce the activation of the PI3K/AKT/Snail signaling pathway. MiR-582 could be a potential molecular therapy target for patients with GC.

Identifying liver metastasis-related hub genes in breast cancer and characterizing SPARCL1 as a potential prognostic biomarker

“…The PI3K/AKT signaling pathway also participated in liver metastasis of various malignant tumors. Indeed, microRNA-582 can promote gastric cancer liver metastasis via the PI3K/AKT/Snail pathway mediated by FOXO-3 ( Xie et al, 2020 ). The c-Met/PI3K/AKT/mTOR axis can activate the liver metastasis-specific cholesterol metabolism pathway in colorectal cancer, providing conditions for tumor cell colonization and growth in the liver ( Zhang et al, 2021a ).…”

Long non‑coding RNA CASC9/microRNA‑590‑3p axis participates in lutein‑mediated suppression of breast cancer cell proliferation

“…They can inhibit or degrade their target mRNAs by binding to the 3′non-coding region of their target gene mRNA ( 18 , 19 ). It has been reported that miRNAs are involved in a series of important processes, such as tumor proliferation, invasion and migration ( 40 , 41 ). Increasing evidence suggest that lncRNAs and miRNAs can interact to cross-regulate the biological processes of tumor cells ( 42 , 43 ).…”

GATA6‑AS1 inhibits ovarian cancer cell proliferation and migratory and invasive abilities by sponging miR‑19a‑5p and upregulating TET2

“…GATA6-AS1 expression has been reported to be downregulated in gastric cancer, where it decreases frizzled class receptor 4 (FZD4) expression by recruiting zeste homolog 2 and inducing trimethylation at lysine 27 of histone H3 of the FZD4 promoter region, inhibiting therefore the Wnt/β-catenin signaling pathway and preventing epithelial-mesenchymal transition ( 7 ). Furthermore, downregulated expression of GATA6-AS1 activates the PI3K/AKT/Snail signaling pathway via regulation of miR-582/FOXO3 axis and subsequently promote the proliferation and metastasis of gastric cancer cells ( 23 ). The present study demonstrated that GATA6-AS1 expression was decreased in OC and that GATA6-AS1 significantly inhibited the proliferation and migratory and invasive abilities of OC cells, confirming that GATA6-AS1 may be a tumor-suppressive lncRNA in OC.…”