Dysregulation of pseudogene/lncRNA-hsa-miR-363-3p-SPOCK2 pathway fuels stage progression of ovarian cancer

Abstract

Objective: Ovarian cancer is one of the most common and lethal cancer types in women. The molecular mechanism of ovarian cancer progression is still unclear.Results: Here, we first reported that expression levels of three genes, GJB2, S100A2 and SPOCK2, were significantly higher in advanced stage than that in early stage of ovarian cancer, and upregulation of them indicated poor prognosis of patients with ovarian cancer. Subsequently, 8, 6 and 20 miRNAs were predicted to target GJB2, S100A2 and SPOCK2, respectively. Among these miRNA-mRNA pairs, hsa-miR-363-3p-SPOCK2 axis was the most potential in suppressing progression of ovarian cancer. Mechanistically, we found that hsa-miR-363-3p-SPOCK2 axis was involved in regulation of actin cytoskeleton. Moreover, 6 pseudogenes and 8 lncRNAs were identified to potentially inhibit hsa-miR-363-3p-SPOCK2 axis in ovarian cancer.Conclusions: Collectively, we elucidate a regulatory role of pseudogene/lncRNA-hsa-miR-363-3p-SPOCK2 pathway in progression of ovarian cancer, which may provide effective therapeutic approaches and promising prognostic biomarkers for ovarian cancer.Materials and methods: Differentially expressed genes (DEGs) in ovarian cancer were first screened using GSE12470, after which DEGs expression were validated using GEPIA. Kaplan-Meier analysis was employed to assess the prognostic values. Potential miRNAs were predicted by seven target prediction databases, and upstream lncRNAs and pseudogenes of hsa-miR-363-3p were forecasted through miRNet or starBase. UALCAN and starBase were used to obtain the co-expressed genes of SPOCK. Enrichment analysis for these co-expressed genes was performed by Enrichr.

MAGI2‐AS3 suppresses MYC signaling to inhibit cell proliferation and migration in ovarian cancer through targeting miR‐525‐5p/MXD1 axis

“…The majority of OV patients always missed the golden opportunity for surgery until the exact diagnosis. Although great improvements have been achieved in therapies for OV patients, the survival of advanced OV patients was unpromising and the prognosis within five years remained disappointing 5 . Therefore, it is critical to get a deep understanding of latent molecular mechanism underlying OV progression.…”

SPOCK2 Serves as a Potential Prognostic Marker and Correlates With Immune Infiltration in Lung Adenocarcinoma

“…In this study, we attempted to systematically explore the expression, prognostic value, correlation with TIICs, and potential mechanism of SPOCK2 in LUAD. In recent studies, SPOCK2 has been shown to be highly expressed in ovarian cancer (Lou et al, 2019) and lowly expressed in prostate cancer (Liu et al, 2019). Its expression increases during lung development (Hadchouel et al, 2020).…”

“…It was reported that TIICs are positively associated with better survival in LUAD, which highlights the importance of TIICs in the clinical outcomes of LUAD patients (Vafadar, 2019). SPARC (osteonectin), cwcv and kazal-like domains proteoglycan 2 (SPOCK2) is known as a secreted protein that is acidic and cysteine-rich, playing a significant role in the development and progression of ovarian cancer, endometrial cancer, and prostate cancer (Liu et al, 2019;Lou et al, 2019;Ren et al, 2019). It was reported that SPOCK2 can prevent viral infection in lung epithelial cells (Ahn et al, 2019).…”

Analysis of long non-coding RNA expression profiles in high-glucose treated vascular endothelial cells

“…Moreover, we identi ed some known lncRNAs may participate in high-glucose treated HUVEC. DAPK1-IT1, DAPK1 intronic transcript 1, has proved involved in cancer progression [41,42] , chemotherapy insensitivity [43] , Atherogenesis [44,45] , etc. In our study, we constructed the coexpression subnet of DAPK1-IT1 and function was analyzed with KEGG pathway (Figure 6), found may function with Terpenoid backbone biosynthesis, Steroid biosynthesis, Vitamin digestion and absorption, Protein processing in endoplasmic reticulum, Phagosome, and some of these pathways have been proved to be involved in the occurrence and development of diabetes.…”