Long Noncoding RNA SNHG7 Activates Wnt/β-Catenin Signaling Pathway in Cervical Cancer Cells by Epigenetically Silencing DKK1

Abstract

Background: Cervical cancer (CC) ranks fourth in cancers that resulted in death among women, accumulating the attention of researchers. It has been ascertained that long noncoding RNAs (lncRNAs) are crucial players in the pathological processes of a host of cancers. And, SNHG7 has been reported to enhance the occurrence of various cancers; however, its function in CC sustains obscure. Aim of the Study: This study explored the function of SNHG7 in CC and further investigates the specific molecular mechanism of SNHG7 in regulating CC. Methods: The levels of SNHG7 in CC cells were reflected by quantitative real-time polymerase chain reaction. The functions of SNHG7 on CC tumorigenesis were explored by colony formation, CCK-8 (Cell Counting Kit-8), EdU (ethynyl deoxyuridine), and Western blot assays. The influences of SNHG7 depletion on the binding of EZH2 to DKK1 promoter and H3K27me3 occupancy in DKK1 promoter were studied by chromatin immunoprecipitation assay. Results: SNHG7 was conspicuously higher expressed in CC cells. Knockdown of SNHG7 was detected to ameliorate the malignant behaviors of CC cells. Importantly, the contribution of SNHG7 to CC development was relied on activated Wnt pathway through DDK1-mediated manner. Furthermore, it was confirmed that SNHG7 silencing weakened the binding of EZH2 to DKK1 promoter as well as the occupancy of H3K27me3 in DKK1 promoter. Conclusions: SNHG7 epigenetically silences DKK1 to exacerbate the malignancy of CC via Wnt/b-catenin signaling pathway.

Expression and Role of Dickkopf-1 (Dkk1) in Tumors: From the Cells to the Patients

“… 92 Demonstration at the cellular level that SNHG7 epigenetically silences Dkk1 through the Wnt/β-catenin signaling pathway. 93 N/A N/A Yes Yes SNHG7 epigenetically silences Dkk1 through the Wnt/β-catenin signaling pathway to exacerbate CC malignancy 97–114 Ovarian cancer STAT3 was demonstrated in EOC cells to regulate tumor progression via miR-92a /β-1 and to interconnect with Wnt/ Dkk1 -catenin signals. 100 TET1 was demonstrated in EOC cells to inhibit the Wnt/β-catenin pathway through demethylation of Dkk1 and thus tumor suppression.…”

“…It has been proven that SNHG7 silences Dkk1 through Wnt/β-catenin signal transduction pathway to aggravate the malignant degree of CC. 93 …”

Potential epigenetic molecular regulatory networks in ocular neovascularization

“…By decreasing miR-543 and increasing Sirt1 expression, SNHG7 prevents high glucose-induced angiogenesis in human retinal endothelial cells (Ke et al, 2019). SNHG7 stimulates the Wnt/-catenin signaling pathway by inhibiting DKK1 production, which primarily controls H3K27 methylation levels by creating a complex with EZH2 in the DKK1 promoter region (Chi et al, 2020). These findings show that epigenetic control of SNHG7 or SNHG1 may play a role in neovascularization.…”

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis

“…A significant number of ncRNAs were confirmed to regulate methylation/demethylation processes by interacting with EZH2. For example, lncRNA SNHG7 (small nucleolar RNA host gene 1) acts as an oncogenic in cervical cancer by recruiting EZH2 to be promoter of the inhibitor of the Wnt/β-catenin signaling DKK , therefore epigenetically enhancing the Wnt/β-catenin signaling [ 109 ]. Interacting with the EZH2, another member of this family, SNHG8 inhibits the expression of tumor suppressor reversion-inducing cysteine-rich protein with kazal motifs (RECK) at the transcriptional level, promoting cervical cancer [ 110 ].…”