Background Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. Methods Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. Results Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. Conclusion This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.

Objective: New vertebral compression fracture (NVCF) occurring after bone cement injection in middle-aged and elderly patients with vertebral compression fracture is very common. Preoperative baseline characteristics and surgical treatment parameters have been widely studied as a risk factor, but the importance of the patients' laboratory indicators has not been thoroughly explored. We aimed to explore the relationship between laboratory indicators and NVCF, and attempt to construct a clinical prediction model of NVCF together with other risk factors.Methods: Retrospective analysis was performed for 200 patients who underwent bone cement injection (percutaneous kyphoplasty or vertebroplasty) for vertebral compression fractures between January 2019 and January 2020. We consulted the relevant literature and collated the factors affecting the occurrence of NVCF. Feature selection of patients with NVCF was optimized using the least absolute shrinkage and selection operator regression model, which was used to conduct multivariable logistic regression analysis, to create a predictive model incorporating the selected features. The discrimination, calibration, and clinical feasibility of the predictive model were assessed using the concordance index (C-index), calibration plots, and decision curve analysis. Internal validation was performed using Bootstrap resampling verification.Results: Time from injury to surgery exceeding 7 days, low osteocalcin levels, elevated homocysteine levels, osteoporosis, mode of operation (percutaneous vertebroplasty), lack of postoperative anti-osteoporosis treatment, and poor diffusion of bone cement were independent risk factors for NVCF in middle-aged and elderly patients with vertebral compression fracture after bone cement injection. The C-index of the nomogram constructed using these seven factors was 0.895, indicating good discriminatory ability. The calibration plot showed that the model was well calibrated. Bootstrap resampling verification yielded a significant C-index of 0.866. Decision curve analysis demonstrated that the greatest clinical net benefit for predicting NVCF after bone cement injection could be achieved with a threshold of 1%-91%. Conclusion:This nomogram can effectively predict NVCF incidence after bone cement injection in middle-aged and elderly patients with vertebral compression fracture, thus aiding clinical decision-making and postoperative management, promoting effective postoperative rehabilitation, and improving the quality of life.

Astragaloside IV (AS IV) and tanshinone (TS IIA) are the main natural components of Salvia miltiorrhiza and Radix Astragali, respectively. The amalgam of TS IIA and AS IV has potential therapeutic value in many inflammation-related diseases. However, the aftereffect of TS IIA and AS IV for lumbar disc herniation is not clear. Although the function of miR-223 in the inflammation-related JAK/STAT pathway is unknown, it is particularly expressed in human degenerative nucleus pulposus cells. This study has investigated the efficacy of the combined application of TS IIA and AS IV in the treatment of intervertebral disc nucleus pulposus cells (NP cells) injured by lipopolysaccharide (LPS). After miR-223 inhibitor imitated NP cells, the state of the JAK family and STAT family was recognized by Western blotting (Western blot, WB) and reverse transcriptase quantitative polymerase chain reaction (qPCR). The shRNA lentivirus interference vector targeting the STAT family was constructed, and the NP cell line stably interfering with the STAT gene was established after transfection. The expression of TNF-α, IL-6, MMP-9, MMP-3, caspase-1, and caspase-3 was detected by lipopolysaccharide (WTNP cells), control virus NP cells, STAT downregulation NP cells, enzyme-linked immunosorbent assay (ELISA), Western blot, and qPCR, respectively. The cell survival rate was detected by flow cytometry and TUNEL staining reverse transcriptase-polymerase chain reaction (qPCR). NP cells were treated with TS IIA and AS IV which had been made into different concentrations, and then, the expression of miR-223, p-STAT1, and p-JAK families was detected by WB Western blotting and qPCR. MiR-223 selectively acts on JAK2/STAT1 pathway, increases the expression of TNF-α, IL-6, MMP-9, MMP-3, caspase3-1, and caspase-3, and induces apoptosis, which can be eliminated by silencing STAT1. TS IIA combined with AS IV could inhibit the expression of miR-223, p-STAT1, and p-JAK2 in NP cells, and they showed a dose-dependent tendency to p-STAT1 and p-JAK2. This study shows that miR-223 promotes the inflammatory response and induces cell injury of NP cells by acting on the JAK2/STAT1 pathway, and the combination of TS IIA and AS IV may protect NP cells by downregulating miR-223 and inhibiting the expression of JAK2 and STAT1.

Background: We analyzed TCGA dataset and observed the downregulation of CTBP1-AS2 in ovarian cancer (OC), while the function of CTBP1-AS2 has only been investigated in diabetes and cardiomyocyte hypertrophy, but not in cancer biology. We therefore analyzed the involvement of CTBP1-AS2 in OC. Result: We found that CTBP1-AS2 was downregulated in OC and predicted poor survival. CTBP1-AS2 in luciferase activity assay interacted with miR-216a, while overexpression of CTBP1-AS2 and miR-216a had no significant effects on the expression of each other. However, increased expression level of PTEN, a target of miR-216a, was observed after CTBP1-AS2 overexpression. Increased proliferation rate of OC cells was observed after the overexpression of miR-216a. CTBP1-AS2 and PTEN overexpression resulted in the reduced proliferation rate of OC cells and reduced effects of miR-216a overexpression. Conclusion: CTBP1-AS2 regulates miR-216a/PTEN to suppress OC cell proliferation.