RACK1 promotes miR-302b/c/d-3p expression and inhibits CCNO expression to induce cell apoptosis in cervical squamous cell carcinoma

Abstract

Background: Cervical squamous cell carcinoma (CSCC) is one of the main causes of cancer-related deaths in women worldwide. The present study was conducted with the main objective of determining the potential role of receptor for activated protein kinase C1 (RACK1) in CSCC through regulation of microRNA (miR)-302b/c/d-3p and Cyclin O (CCNO). Methods: The expression of RACK1, miR-302b/c/d-3p and CCNO in CSCC tissues and cells was measured by RT-qPCR and Western blot analysis. The interaction among RACK1, miR-302b/c/d-3p, and CCNO was determined by dual luciferase reporter assay. Subsequently, effects of RACK1, miR-302b/c/d-3p and CCNO on CSCC cell cycle entry, proliferation and apoptosis were investigated with the use of flow cytometry, EdU, and TUNEL assays. Furthermore, mouse xenograft model of CSCC cells was established to verify the function of RACK1 in vivo. Results: RACK1 and miR-302b/c/d-3p were down-regulated and CCNO was overexpressed in CSCC. CCNO was identified as the target of miR-302b/c/d-3p. Importantly, overexpressed miR-302b-3p, miR-302c-3p or miR-302d-3p or RACK1 enhanced the apoptosis and suppressed the proliferation of CSCC cells in vitro, while inhibiting tumor growth in vivo by targeting CCNO. Conclusions: On all accounts, overexpressed RACK1 could dampen the progression of CSCC through miR-302b/c/d-3p-mediated CCNO inhibition.

The Long Noncoding RNA MAGI1-IT1 Regulates the miR-302d-3p/IGF1 Axis to Control Gastric Cancer Cell Proliferation

“… 19–23 We similarly explore the function of MAGI1‐IT1 as a ceRNA and determined that it was predicted to bind to miR-302d-3p, which is a miRNA that has previously been shown to suppress cervical squamous cell carcinoma tumor growth. 13 We confirmed the ability of MAGI1‐IT1 to sequester miR-302d-3p through both luciferase reporter and RIP assays, and we observed negative correlations between these two RNAs in GC patient tumor tissues. Importantly, miR-302d-3p inhibition was sufficient to reverse the impacts of MAGI1‐IT1 knockdown on GC cell proliferation, confirming that MAGI1‐IT1 regulates GC cell malignancy at least in part by serving as a ceRNA for miR-302d-3p.…”

“…[19][20][21][22][23] We similarly explore the function of MAGI1-IT1 as a ceRNA and determined that it was predicted to bind to miR-302d-3p, which is a miRNA that has previously been shown to suppress cervical squamous cell carcinoma tumor growth. 13 We confirmed the ability of MAGI1-IT1 to sequester miR- Importantly, miR-302d-3p inhibition was sufficient to reverse the impacts of MAGI1-IT1 knockdown on GC cell proliferation, confirming that MAGI1-IT1 regulates…”

“…Many lncRNAs regulate tumor cells by serving as competing endogenous RNAs (ceRNAs) for particular miRNAs. [10][11][12] In cervical squamous cell carcinoma, miR-302d-3p has previously been shown to suppress tumor cell growth, 13 while IGF1 is an important glioma progression inhibitor. 14 Predictive analyses conducted with the TargetScan database suggested that both MAGI1-IT1 and IGF1 shared sequence complementarity with miR-302d-3p, suggesting that a MAGI1-IT1/miR-302d-3p/IGF1 ceRNA regulatory axis may control tumor cell proliferation.…”

Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

“…Ribosomal receptor for activated C-kinase 1 (RACK1) is associated with chemoresistance and tumour growth [ 132 ], with increased levels of RACK1 correlating with tumour progression and fatality [ 133 ]. RACK1 may act via a variety of processes in tumours, including upregulating the assembly and activity of the NLRP3 inflammasome [ 132 , 134 ], miRNAs patterning [ 135 ], and AhR regulation [ 136 ]. Being a ribosomal protein, RACK1 modulates how ribosomes spatiotemporally coordinate patterned gene expression, including local translation process [ 137 ] and centrosome regulation [ 138 , 139 ].…”

Valproic Acid Protects Chondrocytes from LPS-Stimulated Damage via Regulating miR-302d-3p/ITGB4 Axis and Mediating the PI3K-AKT Signaling Pathway

“…Bioinformatics analysis of our study manifested that miR-302d-3p may directly target ITGB4. miR-302d-3p is a member of the miR-302 cluster that was initially found in human embryonic stem cells, which plays a crucial role in endometrial carcinoma (Li et al, 2018), cervical squamous cell cancer (Wang and Chen, 2020), and breast cancer (Sun et al, 2020a). More importantly, Wang et al (2019) have indicated that miR-302d-3p is expressed at higher levels in OA and may hinder the progression of OA via mediating cell viability in chondrocytes.…”