An innovative predictive model for cervical cancer constructed around a gene profile associated with cholesterol metabolism.

Cholesterol metabolism is crucial for cell survival and cancer progression. The prognostic patterns of genes linked to cholesterol metabolism (CMAGs) in CESC, however, have received very little attention in research. From public databases, TCGA-CESC cohorts with mRNA expression patterns and the accompanying clinical information of patients were gathered. Consensus clustering was used to find the molecular subtype connected to cholesterol metabolism. In the TCGA-CESC cohort, a predictive risk model with 28 CMAGs was created using Lasso-Cox regression. The function enrichment analysis between groups with high-and low-risk were investigated by employing GO, KEGG, and GSVA software. The immune cell infiltration was analyzed using ESTIMATE, CIBERSORT, and MCPCOUNTER methods. Finally, we select 7 genes in risk model for further multivariate Cox analysis, and ultimately a hub gene, CHIT1, was identified. Meanwhile, the function of CHIT1 was preliminarily verified in cell and mice tumor model. In conclusion, the abundance of the CHIT1 gene might be beneficial for forecasting the prognosis of CESC, demonstrating that cholesterol metabolism could be a promising treatment target for CESC.

lncRNA FOXD2-AS1 regulates proliferation and apoptosis of cervical cancer cells via targeting miR-506-5p / 中国肿瘤生物治疗杂志

@#Objective: To investigate whether long non-coding RNA (lncRNA) FOXD2-AS1 targets miR-506-5p to regulate proliferation and apoptosis of cervical cancer cells. Methods: Human normal cervical cells Ect1/E6E7 and cervical cancer cell lines (HeLa, Siha and Caski) were cultured in vitro, and the expression levels of FOXD2-AS1 and miR-506-5p in cells were detected by qPCR. The cervical cancer cells with FOXD2-AS1 knockdown and miR-506-5p over-expression were constructed by liposome transfection technology, and the proliferation and apoptosis of cells were detected by MTT assay and flow cytometry respectively, the expression of proliferation-related proteins CyclinD1, p21, p27 and apoptosis-related proteins Bcl-2, BAX, cleaved-capase-3 were detected by WB. Dual luciferase reporter assay was used to verify whether FOXD2-AS1 would target miR-506-5p; and the effects of simultaneous inhibition of FOXD2-AS1 and miR-506-5p on proliferation and apoptosis of cervical cancer cells were also analyzed. Results: Compared with Ect1/E6E7 cells, the expression of FOXD2-AS1 significantly increased while the expression of miR-506-5p significantly decreased in cervical cancer HeLa, Siha and Caski cells (all P<0.01). FOXD2-AS1 knockdown significantly inhibited the protein expressions of CyclinD1, Bcl-2 and cell proliferationin cervical cancer cells, but promoted the protein expressions of p21, p27, BAX, cleavedcapase-3, and cell apoptosis (all P<0.01). miR-506-5p over-expression significantly inhibited the protein expressions of CyclinD1, Bcl2 and cell proliferation in cervical cancer cells, but promoted the protein expressions of p21, BAX, and cell apoptosis (all P<0.01). Dual luciferase reporter gene assay confirmed that FOXD2-AS1 negatively regulated the expression of miR-506-5p in cervical cancer cells (P<0.01). Inhibition of miR-506-5p expression reversed the effect of FOXD2-AS1 knockdown on proliferation and apoptosis of cervical cancer cell (P<0.01). Conclusion: FOXD2-AS1 modulates proliferation and apoptosis of cervical cancer cells by negatively regulating the expression of miR-506-5p.