ABSTRACT
PURPOSE: To explore the effect of circ_0000135/miR-140-3p/PDZ domain containing 1 (PDZK1) on the occurrence and development of cervical cancer. METHODS: Clinical data were collected to verify circ_0000135/miR-140-3p/PDZK1 expression in cervical cancer. mRNA expressions of circ_0000135 and miR-140-3p were detected by real-time quantitative PCR. Correlation between circ_0000135 and miR-140-3p/miR-140-3p and PDZK1 was analyzed in vitro. Protein expression detection in cells was conducted by Western blot; while cell proliferation, invasion and cycle distribution by CCK8 assay, Transwell chamber assay and flow cytometry, respectively. Rescue and animal experiment were performed to verify the effect of circ_0000135/miR-140-3p/PDZK1 on cervical cancer. RESULTS: circ_0000135 and PDZK1 expressions were increased, while those of miR-140-3p were decreased in cervical cancer tissues and cells (both P < 0.05). sh-circ_0000135 group had decreased cell viability, arrested cells in G0/G1 phase, decreased CyclinD1 expression, inhibited cell migration and invasion; sh-circ_0000135 group showed reduced tumor volume, weight, and lower Ki67 expression (all P < 0.05). circ_0000135 had conserved target of miR-140-3p. There was a direct interaction between circ_0000135 and miR-140-3p. miR-140-3p might have direct interaction with PDZK1. sh-circ_0000135 and/or miR-140-3p treatment showed obviously decreased PDZK1 expression, decreased cell activity, arrested cells in G0/G1 phase, downregulated cell migration and invasion; sh-circ_0000135 and/or miR-140-3p mimic treatment showed obviously decreased tumor volume, tumor weight, and Ki67 expression (all P < 0.05). CONCLUSION: circ_0000135 may play an anti-tumor role on the progression of cervical cancer by sponging miR-140-3p to suppress the expression of PDZK1, providing a promising therapeutic target.
Subject(s)
Membrane Proteins , MicroRNAs , RNA, Circular , Uterine Cervical Neoplasms , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Female , Humans , Ki-67 Antigen/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathologyABSTRACT
Osteoporosis is a metabolic bone disorder characterized by low bone mineral density and decreased bone strength, leading to an increased risk of fractures with a consequent increase in morbidity and mortality. The current methods to estimate the fracture risk are very limited. microRNAs (miRNAs) have been considered as good biomarkers for many pathological processes, including osteoporosis. Some circulating miRNAs are associated with regulation of bone formation and differentiation of bone cells. The aim of this study, was to analyze the expression of miRNAs in serum of patients with osteoporosis (nâ¯=â¯20) and healthy controls (nâ¯=â¯20). Expression of 754 miRNAs was analyzed through quantitative real time RT-PCR arrays. Seven miRNAs showed significant differences between groups. The microRNAs miR-23b-3p, miR-140-3p and miR-885-5p were selected based on fold change and p-values (40.5, pâ¯=â¯0.038, 20.7, pâ¯=â¯0.045, and 2.2, pâ¯=â¯0.002; respectively) for validation in independent serum samples from patients with osteopenia (nâ¯=â¯28), osteoporosis (nâ¯=â¯26) and osteoporotic hip fracture (nâ¯=â¯21). After validation, we confirm differences across the groups for miR-23b-3p and miR-140-3p. Our data pointed miR-140-3p and miR-23b-3p as potential biomarkers candidates for osteoporosis in postmenopausal women.