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The aim of this study was to reveal the effect of let‐7b on osteoporosis (OP). Synthetic let‐7b mimics or inhibitors were transfected into MC3T3‐E1 cells. The expression of let‐7b in MC3T3‐E1 and its effect on cell viability, apoptosis, and the apoptosis‐related proteins (Bcl‐2, Bax, and cleaved caspase‐9) were tested by CCK‐8 assay, flow cytometry and Western blot, severally. The osteogenic differentiation markers (Runx2 and Osterix) and Wnt/β‐catenin pathway related markers (β‐catenin and C‐myc) were detected by qRT‐PCR and Western blot. The relationships between let‐7b and cyclin D1 (CCND1) were confirmed by luciferase reporter assay. The differentiation and mineralization of MC3T3‐E1 cells were analyzed by alkaline phosphatase (ALP) activity assay and alizarin red staining. The outcomes indicated that overexpression/ablation of let‐7b repressed/facilitated MC3T3‐E1 cell viability and accelerated/suppressed MC3T3‐E1 cell apoptosis. Besides, a remarkable decrease/augment of Bcl‐2 protein expression and the distinct fortify/reduction of Bax and cleaved caspase‐9 expression levels were observed in let‐7b mimics/inhibitors group in MC3T3‐E1 cells. Moreover, we discovered that let‐7b overexpression/ablation retrained/facilitated the mRNA and protein expression of Runx2 and Osterix. It was confirmed that CCND1 was a downstream target of let‐7b and was negatively modulated by let‐7b. In addition, high‐expression/deficiency of let‐7b inhibited/increased the expression levels of β‐catenin and C‐myc in MC3T3‐E1 cells. Taken together, our study revealed that let‐7b overexpression/depletion repressed/accelerated MC3T3‐E1 cell proliferation, differentiation, and mineralization while promoted/suppressed MC3T3‐E1 cell apoptosis through targeting CCND1, which might be adjusted by Wnt/β‐catenin pathway. Our findings might offer a basis for developing novel targets for OP treatment.

Background: MicroRNA-1258 ( miR-1258 ) has been shown to play an anti-cancer role in a variety of cancers, but its relationship with papillary thyroid cancer (PTC) has not been reported. The emphasis of this research was to reveal the biological function of miR-1258 in PTC and its potential mechanisms. Material and methods: We measured miR-1258 expression in PTC cells and the transfection efficiency of miR-1258 mimic and miR-1258 inhibitor by quantitative real-time PCR (qRT-PCR) assay. Cell Counting Kit-8 assay (CCK8) and Transwell experiments were conducted to examine the influences of altering miR-1258 expression on the viability, migration, and invasion of PTC cells. Bioinformatics prediction and dual-luciferase experiment were performed to verify the target gene of miR-1258 . Finally, we carried out a rescue assay to verify whether the regulation of miR-1258 on the biological behaviour of PTC cells needs to be achieved by regulating TMPRSS4 . Results: The outcomes revealed that miR-1258 was lowly expressed in PTC cell lines and miR-1258 showed the lowest expression in KTC-1 and the highest expression in B-CPAP among all tested PTC cell lines. Overexpression of miR-1258 inhibited KTC-1 cell viability and ability to migrate and invade, whereas inhibition of miR-1258 in B-CPAP cells has the opposite effect. Furthermore, we affirmed that miR-1258 can directly target TMPRSS4 , and miR-1258 can reduce the biological malignant behaviour of PTC cells via regulation of TMPRSS4 . Conclusion: Taken together, our research raised the possibility that miR-1258 was an anti-oncogene, which exerts its anti-cancer function by targeting TMPRSS4 . Hence, it may be possible to treat PTC by targeting the miR-1258/TMPRSS4 axis in the future.

Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner syndrome is a segmental progeroid syndrome whose presentation resembles accelerated aging. The most common causes of death for WS patients are atherosclerosis and cancer. A 40-year-old female presented with short stature, bird-like facies, canities with alopecia, scleroderma-like skin changes, and non-healing foot ulcers. The patient reported a history of delayed puberty, abortion, hypertriglyceridemia, and juvenile cataracts. A clinical diagnosis of WS was made and subsequently confirmed. We discovered two WRN gene mutations in the patient, Variant 1 was the most common WRN mutation, nonsense mutation (c.1105C>T:p.R369Ter) in exon 9, which caused a premature termination codon (PTC) at position 369. Variant 2 was a frameshift mutation (c.1134delA:p.E379KfsTer5) in exon 9, which caused a PTC at position 383 and has no published reports describing. Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia). Doctors must be cognizant of early manifestations of WS and treatment options.

ObjectiveTo explore potential functional biomarkers in diabetes mellitus (DM) by utilizing gene pathway cross-talk.MethodsFirstly, potential disrupted pathways that were enriched by differentially expressed genes (DEGs) were identified based on biological pathways downloaded from the Ingenuity Pathways Analysis (IPA) database. In addition, we quantified the pathway crosstalk for each pair of pathways based on Discriminating Score (DS). Random forest (RF) classification was then employed to find the top 10 pairs of pathways with a high area under the curve (AUC) value between DM samples versus normal samples based on 10-fold cross-validation. Finally, a Monte Carlo Cross-Validation was applied to demonstrate the identified pairs of pathways by a mutual information analysis.ResultsA total of 247 DEGs in normal and disease samples were identified. Based on the F-test, 50 disrupted pathways were obtained with false discovery rate (FDR) < 0.01. Simultaneously, after calculating the DS, the top 10 pairs of pathways were selected based on a higher AUC value as measured by RF classification. From the Monte Carlo Cross-Validation, we considered the top 10 pairs of pathways with higher AUC values ranked for all 50 bootstraps as the most frequently detected ones.ConclusionThe pairs of pathways identified in our study might be key regulators in DM.