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MicroRNAs (miRNAs), a class of short, single-stranded non-coding RNAs, regulate and control gene expression in eukaryotes by degrading mRNA at the post-transcriptional level. Regulation by miRNAs involves a plethora of biological processes, such as cell differentiation, proliferation, metastasis, metabolism, apoptosis, tumorigenesis and others. miRNAs also represent a powerful tool in disease diagnosis and prognosis. The miR-17-92 cluster, one of the most extensively investigated microRNA clusters, comprises six mature miRNA members, including miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a. Originally identified as being involved in tumorigenesis, it is currently evident that the expression of the miR-17-92 cluster is upregulated in a wide range of tumor cells and cancer types; thus, this cluster has been identified as a potential oncogene. Considering the growing interest in the field of miR-17-92 research, we herein review recent advances in the expression and regulation of this cluster in various cancer cells, discuss the proposed mechanism of action for tumorigenesis and tumor development, and propose clinical and therapeutic applications for miR-17-92 cluster members, such as potential cancer biomarkers.

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AimThe aim of this study was to estimate the prevalence, awareness, treatment, and control of dyslipidemia in Xinjiang, China.MethodStratified sampling method was used to select a representative sample of the general population including Chinese Han, Uygur, and Kazak in this geographic area. Seven cities were chosen. Based on the government records of registered residences, one participant was randomly selected from each household. The eligibility criterion for the study was ≥ 35 years of age.ResultsA total of 14,618 participants (5,757 Han, 4,767 Uygur, and 4,094 Kazak), were randomly selected from 26 villages in 7 cities. The prevalence of dyslipidemia was 52.72% in the all participants. The prevalence of dyslipidemia was higher in Han than that in the other two ethnic (58.58% in Han, 48.27% in Uygur, and 49.60% in Kazak, P < 0.000). The prevalence of dyslipidemia was higher in men than that in women (56.4% vs. 49.3%, P < 0.000). Among the participants with dyslipidemia, the proportion of those who aware, treat, control of dyslipidemia were 53.67%, 22.51%, 17.09% in Han, 42.19%, 27.78%, 16.20% in Uygur, 37.02%, 21.11%, 17.77% in Kazak.ConclusionDyslipidemia is highly prevalent in Xinjiang. The proportion of participants with dyslipidemia who were aware, treated, and controlled is unacceptably low. These results underscore the urgent need to develop national strategies to improve the prevention, detection, and treatment of dyslipidemia in Xinjiang.

The present study aimed to determine the expression profile and significance of microRNA-140-3p (miR-140-3p) in breast cancer (BC). miR-140-3p expression in BC tumor tissues and cell lines was measured by reverse transcription-quantitative polymerase chain reaction. Luciferase activity reporter assay and western blotting were used to assess the effect of miR-140-3p expression on tripartite motif 28 (TRIM28). Cell growth, migration, and invasion were assessed by Cell Counting Kit-8 assay, wound-healing assay and Transwell invasion assay, respectively. miR-140-3p expression was significantly reduced in BC tumor tissues compared with in adjacent normal tissues. Additionally, low miR-140-3p expression was found to predict poor prognosis of patients with BC. TRIM28 expression was significantly reduced by miR-140-3p overexpression in BC cell lines, and was inversely correlated with miR-140-3p in BC tissues. Overexpression of miR-140-3p also inhibited cell proliferation, migration and invasion compared with in the control group. In conclusion, the present study revealed that miR-140-3p inhibited the progression of BC partially by regulating TRIM28.

Background T cells expressing a chimeric antigen receptor (CAR) engineered to target CD19 can treat leukemia effectively but also increase the risk of complications such as cytokine release syndrome (CRS) and CAR T cell related encephalopathy (CRES) driven by interleukin-6 (IL-6). Here, we investigated whether IL-6 knockdown in CART-19 cells can reduce IL-6 secretion from monocytes, which may reduce the risk of adverse events. Methods Supernatants from cocultures of regular CART-19 cells and B lymphoma cells were added to monocytes in vitro, and the IL-6 levels in monocyte supernatants were measured 24 h later. IL-6 expression was knocked down in regular CART-19 cells by adding a short hairpin RNA (shRNA) (termed ssCART-19) expression cassette specific for IL-6 to the conventional CAR vector. Transduction efficiency and cell proliferation were measured by flow cytometry, and cytotoxicity was measured by evaluating the release of lactate dehydrogenase into the medium. Gene expression was assessed by qRT-PCR and RNA sequencing. A xenograft leukemia mouse model was established by injecting NOD/SCID/γc-/- mice with luciferase-expressing B lymphoma cells, and then the animals were treated with regular CART-19 cells or ssCART-19. Tumor growth was assessed by bioluminescence imaging. Results Both recombinant IL-6 and CART-19 derived IL-6 significantly triggered IL-6 release by monocytes. IL-6 knockdown in ssCART-19 cells dramatically reduced IL-6 release from monocytes in vitro stduy. In vivo study further demonstrated that the mice bearing Raji cells treated with ssCART-19 cells showed significant lower IL-6 levels in serum than those treated with regular CART-19 cells, but comparable anti-tumor efficacy between the animal groups. Conclusion CAR T-derived IL-6 is one of the most important initiators to amplify release of IL-6 from monocytes that further drive sCRS development. IL-6 knockdown in ssCART-19 cells by shRNA technology provide a promising strategy to improve the safety of CAR T cell therapy.

BackgroundThe aim of this study was to estimate the prevalence and distribution of type 2 diabetes and to determine the status of type 2 diabetes awareness, treatment, and control in Xinjiang, China. Our data came from the Cardiovascular Risk Survey (CRS) study designed to investigate the prevalence and risk factors for cardiovascular diseases in Xinjiang from October 2007 to March 2010. A total of 14 122 persons (5583 Hans, 4620 Uygurs, and 3919 Kazaks) completed the survey and examination. Diabetes was defined by the American Diabetes Association 2009 criteria.Methodology/Principal FindingsOverall, 9.26% of the Han, 6.23% of the Uygur, and 3.65% of the Kazak adults aged ≥35 years had diabetes. Among diabetes patients, only 53.0% were aware of their blood glucose level, 26.7% were taking hypoglycemic agents, and 10.4% achieved blood glucose control in Han, 35.8% were aware of their blood glucose level, 7.3% were taking hypoglycemic agents, and 3.13% achieved blood glucose control in Uygur, and 23.8% were aware of their blood glucose level, 6.3% were taking hypoglycemic agents, and 1.4% achieved blood glucose control in Kazak, respectively.Conclusions/SignificanceOur results indicate that diabetes is highly prevalent in Xinjiang. The percentages of those with diabetes who are aware, treated, and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of diabetes in Xinjiang, the west China.

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