SCARA5 suppresses the proliferation and migration, and promotes the apoptosis of human retinoblastoma cells by inhibiting the PI3K/AKT pathway

Abstract

Retinoblastoma (RB) is the most common ocular malignancy that occurs during childhood. Scavenger receptor class A member 5 (SCARA5) is considered to function as an anti-oncogene in several types of malignant tumor. The present study investigated the functional role and underlying mechanism of SCARA5 in human RB cells. Reverse transcription-quantitative PCR and western blotting were used to detect the relative expression levels of SCARA5 in four human RB cell lines. In addition, transfection was performed to either knockdown or induce overexpression of SCARA5 in human RB Y79 cells. The proliferation, migration and apoptosis of RB cells was then measured by Cell Counting Kit 8 assay, 5-ethynyl-2'-deoxyuridine assay, clone formation assay, Transwell assay, Hoechst staining and TUNEL staining, respectively. Western blotting was performed to detect changes in the expression levels of key proteins involved in the PI3K/AKT and apoptotic pathways. The present study revealed that SCARA5 was expressed at lower levels in four tumorigenic human RB cell lines compared with in a human retinal pigment non-tumorigenic cell line. Functional analysis demonstrated that overexpression of SCARA5 decreased the proliferation and migration, and promoted the apoptosis of human RB cells in vitro, whereas in vivo experiments revealed a decrease in RB progression following SCARA5 overexpression. In addition, overexpression of SCARA5 inhibited phosphorylated (p)-PI3K and p-AKT expression, and knockdown of SCARA5 increased p-PI3K and p-AKT expression; however, no changes in total PI3K and AKT expression were observed. Bcl-2 exhibited similar changes in expression to those displayed by p-PI3K and p-AKT, whereas Bax and cleaved caspase-3 exhibited trends in expression that were the opposite to those shown by p-PI3K and p-AKT. In conclusion, the present results demonstrated that SCARA5 could inhibit the proliferation and promote the apoptosis of RB cell lines by suppressing the PI3K/AKT signaling pathway, thus suggesting a novel strategy for treating RB.

SCARA5 induced ferroptosis to effect ESCC proliferation and metastasis by combining with Ferritin light chain

“…Disorder of SCARA5 was believed to be involved in the malignancy of multiple tumors such as, Zheng et al found that decreasing SCARA5 promotes Renal Cell Carcinoma proliferation [31]; Wang et al found that SCARA5 could suppress the proliferation and promote the apoptosis of retinoblastoma cells by inhibiting the PI3K/AKT pathway [32]. And some researches revealed that SCARA5 was essential for tumor metastasis and invasion [33][34][35].…”

Stem-Cell-Derived Extracellular Vesicles: Unlocking New Possibilities for Treating Diminished Ovarian Reserve and Premature Ovarian Insufficiency

“…FGF2 produced by the cumulus cells activates an autocrine/paracrine FGF2/FGFR loop within the cumulus-oocyte complex to promote oocyte maturation and meiosis [137]. IGF-1 acts through the PI3K/AKT pathway and regulates downstream proteins that may improve ovarian function [138,139]. Thus, growth factors secreted by stem cells can regulate ovarian function and follicular development.…”

Publication Trends of Research on Retinoblastoma During 2001–2021: A 20-Year Bibliometric Analysis

“…Furthermore, circular RNAs (circRNAs) can also serve as ceRNAs to regulate the proliferation and migration of retinoblastoma cells, such as the circDHDDS/miR-361-3p/WNT3A axis and Circ_0000034/miR-361-3p/ADAM19 axis (47,48). In addition to non-coding RNAs, cyclin-dependent kinase regulatory subunit 1B (CKS1B) downregulation hinders the proliferation, migration, and angiogenesis of retinoblastoma cells through the MEK/ ERK signaling pathway, and an anti-oncogene scavenger receptor class A member 5 (SCARA5) was reported to prevent the proliferation and migration of retinoblastoma cell lines by suppressing the PI3K/AKT signaling pathway (49,50). Studies revealing the mechanisms of the pathogenesis and evolution of retinoblastoma will provide a promising theoretical basis for clinical therapy.…”