Long noncoding RNA LINC01234 silencing exerts an anti-oncogenic effect in esophageal cancer cells through microRNA-193a-5p-mediated CCNE1 downregulation.

BACKGROUND: Long non-coding RNAs (lncRNAs) are transcribed pervasively in the genome and act to regulate chromatin remodeling and gene expression. Dysregulated lncRNA expression has been reported in many cancers, but the role of lncRNAs in esophageal cancer (EC) has so far remained poorly understood. In this study, we aimed to understand the effect of lncRNA LINC01234 on EC development through competitively binding to microRNA-193a-5p (miR-193a-5p). METHODS: The Gene Expression Omnibus (GEO) database was used for microarray-based EC expression profiling. Gain- and loss-of-function analyses were carried out in human EC-derived Eca-109 and EC9706 cells. Expression analyses of miR-193a-5p, LINC01234, CCNE1, caspase-3, p21, Bax, cyclinD1 and Bcl-2 were performed using RT-qPCR and Western blotting. Cell proliferation, colony formation and apoptosis analyses were carried out using MTT, Hoechst 33258 and flow cytometry assays. A xenograft EC model in nude mice was used to evaluate in vivo tumor growth and CCNE1 expression. RESULTS: Microarray-based analyses revealed that LINC01234 expression was increased in primary EC samples, whereas that of miR-193a-5p was decreased. We found that CCNE1 was a target of miR-193a-5p and that LINC01234, in turn, sponges miR-193a-5p. After treatment with si-LINC01234 or miR-193a-5p mimic, EC cells (Eca-109 and EC9706) exhibited cyclinD1 and Bcl-2 downregulation, and caspase-3, p21, Bax and cleaved caspase-3 upregulation. LINC01234 silencing or miR-193a-5p upregulation resulted in decreased proliferation and colony formation, and increased apoptosis of EC cells. In addition, LINC01234 silencing or miR-193a-5p upregulation resulted in reduced in vivo EC tumor growth and CCNE1 expression in nude mice. CONCLUSIONS: We found that silencing of LINC01234 suppresses EC development by inhibiting CCNE1 through competitively binding to miR-193a-5p, which suggests that LINC01234 may represent a novel target for EC therapy.

[Efficacy and safety of Buyang Huanwu Decoction for early-stage diabetic nephropathy: a Meta-analysis].

Buyang Huanwu Decoction(BHD) has the effect in benefiting Qi and activating blood circulation,and is the representative prescription for benefiting Qi and activating blood. At present,it is used for treatment of early diabetic nephropathy. However,its efficacy and safety remained to be verified. Therefore,this study aims to systematically evaluate the efficacy and safety of Buyang Huanwu Decoction for early-stage diabetic nephropathy. Data of randomized controlled trials(RCTs) of Buyang Huanwu Decoction for earlystage diabetic nephropathy were collected through the retrieval of electronic databases,including PubMed,EMbase,the Cochrane Library,CBM,CNKI,VIP and Wan Fang Data from inception to September 16,2018. Two reviewers independently screened out literatures,extracted data,and assessed the risk of bias. And then Meta-analysis was conducted by Rev Man 5. 3 software. A total of 15 RCTs involving 1 402 patients were included. The results of Meta-analysis indicated that Buyang Huanwu Decoction and conventional treatment group(combination treatment group) were superior to conventional treatment group in reducing 24 h urinary albumin excretion rates(MD =-40. 23,95% CI[-71. 25,-9. 21],P = 0. 01) and total cholesterol(MD =-0. 75,95% CI[-1. 02,-0. 48],P <0. 000 01). The effects of the two groups in reducing serum creatinine were similar(MD =-1. 48,95%CI[-4. 48,1. 53],P = 0. 34).However,the reduction of triglyceride was affected by the course of treatment. The effects were similar in less than or equal to eight weeks(MD =-0. 33,95%CI[-0. 97,0. 31],P = 0. 31),whereas the combination group was superior to the conventional treatment group in 12 weeks(MD =-0. 30,95%CI[-0. 58,-0. 22],P = 0. 03) and more than or equal to 16 weeks(MD =-0. 49,95% CI[-0. 9,-0. 08],P= 0. 02). There were no significant difference in adverse events between the two groups(OR= 1. 38,95%CI[0. 28,6. 8],P = 0. 69). The results showed that combination treatment group has a significantly higher efficacy on early diabetic nephropathy.The above conclusion shall be verified with more high-quality RCTs because of the low quality of the included studies.

Real-time observation of nucleoplasmin-mediated DNA decondensation and condensation reveals its specific functions as a chaperone.

Fertilization requires decondensation of promatine-condensed sperm chromatin, a dynamic process serving as an attractive system for the study of chromatin reprogramming. Nucleoplasmin is a key factor in regulating nucleosome assembly as a chaperone during fertilization process. However, knowledge on nucleoplasmin in chromatin formation remains elusive. Herein, magnetic tweezers (MT) and a chromatin assembly system were used to study the nucleoplasmin-mediated DNA decondensation/condensation at the single-molecular level in vitro. We found that protamine induces DNA condensation in a stepwise manner. Once DNA was condensed, nucleoplasmin, polyglutamic acid, and RNA could remove protamine from the DNA at different rates. The affinity binding of the different polyanions with protamine suggests chaperone-mediated chromatin decondensation activity occurs through protein-protein interactions. After decondensation, both RNA and polyglutamic acid prevented the transfer of histones onto the naked DNA. In contrast, nucleoplasmin is able to assist the histone transfer process, even though it carries the same negative charge as RNA and polyglutamic acid. These observations imply that the chaperone effects of nucleoplasmin during the decondensation/condensation process may be driven by specific spatial configuration of its acidic pentamer structure, rather than by electrostatic interaction. Our findings offer a novel molecular understanding of nucleoplasmin in sperm chromatin decondensation and subsequent developmental chromatin reprogramming at individual molecular level.

[Expression of autophagy-related genes Beclin1 and MAPLC3 in non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Some studies have indicated that the down-regulation of autophagy-related genes might result in tumorigenesis. This study was to investigate the expression and significance of autophagy-related genes Beclin1 and microtubule-associated protein 1 light chain 3 (MAPLC3) in human non-small cell lung cancer (NSCLC). METHODS: The expression of Beclin1 and MAPLC3 in tumor tissues, adjacent non-cancerous tissues, and normal tissues from 72 specimens of NSCLC were detected by immunofluorescence staining, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The positive rates of Beclin1 and MAPLC3 were significantly lower in NSCLC tissues than in adjacent non-cancerous tissues and normal tissues (8.3% vs. 100% and 100% for Beclin1, chi2=199.40, P<0.01; 13.9% vs. 100% and 100%for MAPLC3, chi2=182.75, P<0.01). The mRNA levels of Beclin1 and MAPLC3 were significantly lower in NSCLC tissues than in adjacent non-cancerous tissues and normal tissues (1.30+/- 0.44 vs. 1.69+/-0.59 and 1.67+/-0.48 for Beclin1, F=6.6, P<0.01; 4.55+/-1.23 vs. 6.73+/-1.31 and 6.90+/-1.87 for MAPLC3, F=14.1, P<0.01). The protein levels of Beclin1 and MAPLC3 were significantly lower in NSCLC tissues than in adjacent non-cancerous tissues and normal tissues (3.49+/-0.72 vs. 5.31+/-1.16 and 6.33+/-1.58 for Beclin1, F=9.73, P<0.01; 2.43+/-0.35 vs. 3.12+/-0.73 and 3.41+/-0.90 for MAPLC3, F=3.22, P=0.04). CONCLUSION: The expression of autophagy-related genes are down-regulated in NSCLC, which may relate to tumorigenesis and development of lung cancer.