MicroRNA-330-5p promotes the development of osteosarcoma by regulating SPRY2.

OBJECTIVE: MicroRNA is an endogenous, non-coding small RNA that has a significant role in regulating organisms and pathology. Previous studies have demonstrated that microRNA-330-5p was a cancer-promoting gene. However, the role of microRNA-330-5p in osteosarcoma (OS) has not been reported. The aim of this work was to explore the characteristics of microRNA-330-5p expression in OS, and to further study its expression in OS and its relationship with clinicopathological parameters and prognosis. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to investigate the expression of microRNA-330-5p in 48 pairs of OS tissues and paracancer tissues, and to analyze the relationship between the expression of microRNA-330-5p and OS clinical indicators and patient prognosis. Meanwhile, qRT-PCR was performed to verify the microRNA-330-5p expression in OS cells. In addition, the microRNA-330-5p knockdown expression model was constructed using lentivirus in OS cell lines U2OS and MG63. The effects of microRNA-330-5p on the biological function of OS cells were analyzed by Cell Counting Kit-8 (CCK-8) and transwell experiments. The potential mechanism was explored by Western blot. RESULTS: In this paper, qRT-PCR results showed that the expression of microRNA-330-5p in OS was higher than that in paracancer tissues, and the difference was statistically significant. Compared with microRNA-330-5p low expression group, patients with high expression of microRNA -330-5p had a higher prevalence of distant metastasis and a lower overall survival rate. In vitro experiment showed that the proliferation, invasion and metastasis abilities of the cells in the microRNA-330-5p silencing group were markedly decreased compared with the negative control group (NC group). Western blot results demonstrated that microRNA-330-5p inhibitor can activate SPRY2 and regulate the expression of key proteins, such as p-Smad2, p-Smad3, TGF-ß1, MMP9 and Vimentin in the TGF-ß1/Smad signaling pathway. It was found that there was a mutual regulation between microRNA-330-5p and SPRY2, which promoted the malignant progression of OS. CONCLUSIONS: The expression of microRNA-330-5p was markedly increased in OS, which was associated with distant metastasis and poor prognosis. Furthermore, we found that microRNA-330-5p may promote the vicious progression of OS by inter-modulating SPRY2 and the TGF-ß1/Smad signaling pathways.

MiRNA-7b-5p attenuates the progression of osteoporosis by inhibiting adipose differentiation of hMSCs via regulating IRS2.

OBJECTIVE: To elucidate whether microRNA-7b-5p (miRNA-7b-5p) could inhibit adipose differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) through regulating IRS2, thereby alleviating the progression of osteoporosis. MATERIALS AND METHODS: Expression levels of miRNA-7b-5p and IRS2 in hMSCs at different stages of adipogenic differentiation and osteogenic differentiation were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. After transfection of miRNA-7b-5p mimic or pcDNA-IRS2 in hMSCs, lipid droplet formation in cells was observed by oil red O staining. Expressions of C/EBPα and PPARγ were detected by qRT-PCR and Western blot. The potential target gene of miRNA-7b-5p was predicted by bioinformatics and verified by dual-luciferase reporter gene assay. Finally, expressions of IRS2 in hMSCs transfected with miRNA-7b-5p-NC, miRNA-7b-5p mimic or co-transfected with miRNA-7b-5p mimic and pcDNA-IRS2 were examined. RESULTS: Expressions of miRNA-7b-5p and IRS2 gradually decreased with the prolongation of adipogenic differentiation, but increased during osteogenic differentiation of hMSCs. Transfection of miRNA-7b-5p mimic reduced oil red O staining after adipogenic differentiation and downregulated mRNA and protein levels of C/EBPα and PPARγ. Transfection of pcDNA-IRS2 increased oil red O staining after osteogenic differentiation and upregulated mRNA and protein levels of C/EBPα and PPARγ. Dual-luciferase reporter gene results showed that miRNA-7b-5p could bind to IRS2. Overexpression of IRS2 reversed the downregulated mRNA and protein levels of adipogenic-related genes C/EBPα and PPARγ due to the overexpression of miRNA-7b-5p. CONCLUSIONS: MiRNA-7b-5p inhibits the adipogenic differentiation of hMSCs through IRS2, thus alleviating the development of osteoporosis.

[A single-center clinical analysis of 65 cases of pseudomyxoma peritonei from appendiceal origin in the early stage].

Objective: To analyze the efficacy and safety of cytoreduction surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) in the early stage. Methods: The clinical data, including pathological features, recurrence and survival of 65 PMP patients in the early stage underwent CRS combined with HIPEC in Aerospace Center Hospital from January, 2011 to December, 2018 were retrospectively analyzed. Results: 65 patients with early stage PMP underwent CRS+ HIPEC. Among these patients, 25 were males and 40 were females, and the mean age was 52.5 years. The median peritoneal cancer index was 3 (0-16). The score of completeness of cytoreduction (CC) of 63 patients (96.9%) was 0, and 2 patients (3.1%) was 1. No perioperative death occurred, the incidence of surgical complications above grade 3 was 3.1%. Three patients relapsed during the follow-up period, including 1 patient with low-grade PMP, 1 patient with high-grade PMP, and 1 patient with high-grade PMP accompanied by signet ring cell. The 5-year disease-free survival rate of the whole group was 92.4%. Conclusions: PMP patients in the early stage treated by CRS combined with HIPEC can achieve benefit and safety. A close long-term follow-up is necessary.