Retracted: MicroRNA-373 promotes the development of endometrial cancer by targeting LATS2 and activating the Wnt/β-Catenin pathway

In the female reproductive tract, endometrial cancer is the most common malignant tumor. Recently, the specific functions of many miRNAs have been identified in endometrial cancer. However, the contradictory effects of microRNA-373 (miR-373) in different human cancers draw our attention. In the present research, upregulation of miR-373 was identified in endometrial cancer which predicted poor prognosis. Moreover, upregulation of miR-373 promoted the migration, invasion, and proliferation of endometrial cancer cells. To further confirm that results, the EMT and Wnt/β-Catenin pathways were also investigated, which were promoted by overexpression of miR-373. Then, we further investigate the downstream factor, large tumor suppressor kinase 2 (LATS2) which was inhibited by miR-373. LATS2 was verified as a direct target gene of miR-373 through luciferase reporter assay. Especially, the facilitation of miR-373 for cell proliferation, migration and invasion was impaired by LATS2. Taken together, miR-373 promotes the progression of endometrial cancer through targeting LATS2 and promoting EMT and Wnt/β-Catenin pathway.     

miR-195通过下调IGF-1R的表达抑制胶质母细胞瘤的增殖和迁移

目的:探讨miR-195对胶质母细胞瘤(Glioblastoma,GBM)增殖和迁移的影响,并阐明其分子调控机制。方法:采用qRT-PCR检测不同级别胶质瘤中miR-195的表达。将miR-195转染至胶质瘤U251细胞后,应用qRT-PCR验证转染效率,MTT及划痕实验检测U251细胞的增殖及迁移能力的改变,qRT-PCR及Western blot检测胰岛素样生长因子1受体(Insulin-like growth factor 1receptor, IGF-1R)的mRNA和蛋白表达;利用质粒转染过表达miR-195后,同时过表达IGF-1R,再应用MTT及划痕实验检测U251细胞的增殖及迁移能力的变化。结果:随着胶质瘤级别的增加,miR-195的表达逐渐降低,各级别胶质瘤中miR-195的表达差异有统计学意义(P0.05)。体外转染miR-195至U251细胞24、48、72 h后,转染组细胞活力和迁移能力均较对照组显著降低(P0.05),细胞中IGF-1R的mRNA和蛋白的表达也明显减少(P0.05);通过转染IGF-1R过表达质粒可显著逆转miR-195过表达对U251细胞增殖及迁移的抑制作用。结论:miR-195可能通过下调IGF-1R的表达,进而抑制胶质母细胞瘤的增殖和迁移。     

Isolation and Characterization of a Hybrid Respiratory Supercomplex Consisting of Mycobacterium tuberculosis Cytochrome bcc and Mycobacterium smegmatis Cytochrome aa3

Recently, energy production pathways have been shown to be viable antitubercular drug targets to combat multidrug-resistant tuberculosis and eliminate pathogen in the dormant state. One family of drugs currently under development, the imidazo[1,2-a]pyridine derivatives, is believed to target the pathogen''s homolog of the mitochondrial bc₁ complex. This complex, denoted cytochrome bcc, is highly divergent from mitochondrial Complex III both in subunit structure and inhibitor sensitivity, making it a good target for drug development. There is no soluble cytochrome c in mycobacteria to transport electrons from the bcc complex to cytochrome oxidase. Instead, the bcc complex exists in a “supercomplex” with a cytochrome aa₃-type cytochrome oxidase, presumably allowing direct electron transfer. We describe here purification and initial characterization of the mycobacterial cytochrome bcc-aa₃ supercomplex using a strain of M. smegmatis that has been engineered to express the M. tuberculosis cytochrome bcc. The resulting hybrid supercomplex is stable during extraction and purification in the presence of dodecyl maltoside detergent. It is hoped that this purification procedure will potentiate functional studies of the complex as well as crystallographic studies of drug binding and provide structural insight into a third class of the bc complex superfamily.     

Saturated fatty acid-induced miR-195 impairs insulin signaling and glycogen metabolism in HepG2 cells

MicroRNAs (miRNAs) play an important role in insulin signaling and insulin secretion, but the role of miRNAs in the association between obesity and hepatic insulin resistance is largely unknown. This study reports that saturated fatty acid (SFA) and high fat diet (HFD) significantly induce miR-195 expression in hepatocytes, and that the insulin receptor (INSR), not insulin receptor substrate-1 (IRS-1), is a direct target of miR-195. Furthermore, the ectopic expression of miR-195 suppresses the expression of INSR, thereby impairing the insulin signaling cascade and glycogen synthesis in HepG2 cells. These findings suggest that the dysregulation of miR-195 by SFA is a detrimental factor for hepatic insulin sensitivity.     

MiR-517a-3p accelerates lung cancer cell proliferation and invasion through inhibiting FOXJ3 expression

Aims

Aberrant expression of microRNAs (miRNAs) results in alterations of various biological processes (e.g., cell cycle, cell differentiation, and apoptosis) and cell transformation. Altered miRNAs expression was associated with lung carcinogenesis and tumor progression. This study aimed to investigate the function and underlying molecular events of miR-517a-3p on regulation of lung cancer cell proliferation and invasion.

Main methods

Transfected miR-517a-3p mimics or inhibitors into 95D and 95C cells respectively, the effects of miR-517a-3p on lung cancer cell proliferation, migration, and invasion were detected. Bioinformatics software forecasted potential target genes of miR-517a-3p and dual luciferase reporter gene system and western blot verified whether miR-517a-3p regulates FOXJ3 expression directly.

Key findings

MiR-517a-3p was differentially expressed in lung cancer 95D and 95C cell lines that have different metastatic potential. Manipulation of miR-517a-3p expression changed lung cancer cell proliferation, migration and invasion capacity. MiR-517a-3p directly regulated FOXJ3 expression by binding to FOXJ3 promoter.

Significance

This study demonstrated that miR-517a-3p promoted lung cancer cell proliferation and invasion by targeting of FOXJ3 expression.     

Attenuated neuroprotective effect of riboflavin under UV-B irradiation via miR-203/c-Jun signaling pathway in vivo and in vitro

Background

Riboflavin (RF) or vitamin B2 is known to have neuroprotective effects. In the present study, we report the attenuation of the neuroprotective effects of RF under UV-B irradiation. Preconditioning of UV-B irradiated riboflavin (UV-B-RF) showed attenuated neuroprotective effects compared to that of RF in SH-SY5Y neuroblostoma cell line and primary cortical neurons in vitro and a rat model of cerebral ischemia in vivo.

Results

Results indicated that RF pretreatment significantly inhibited cell death and reduced LDH secretion compared to that of the UV-B-RF pretreatment in primary cortical neuron cultures subjected to oxygen glucose deprivation in vitro and cortical brain tissue subjected to ischemic injury in vivo. Further mechanistic studies using cortical neuron cultures revealed that RF treatment induced increased miR-203 expression which in turn inhibited c-Jun expression and increased neuronal cell survival. Functional assays clearly demonstrated that the UV-B-RF preconditioning failed to sustain the increased expression of miR-203 and the decreased levels of c-Jun, mediating the neuroprotective effects of RF. UV-B irradiation attenuated the neuroprotective effects of RF through modulation of the miR-203/c-Jun signaling pathway.

Conclusion

Thus, the ability of UV-B to serve as a modulator of this neuroprotective signaling pathway warrants further studies into its role as a regulator of other cytoprotective/neuroprotective signaling pathways.     

miR-200a 及AFP 在肝癌、肝硬化患者血清中表达比较分析*

目的:分析miR-200a及AFP在肝癌、肝硬化患者血清中的表达水平并进行比较,探索其成为肝癌早期诊断血清标志物的可能性。方法:临床收集肝正常、肝硬化、肝癌患者血液标本。运用实时定量PCR技术检测血清miR-200a的相对表达情况,血清AFP水平从临床资料中提取。结果:临床标本分析结果显示,miR-200a在肝硬化及肝癌患者中均显著下调(P<0.05),AFP仅在肝癌患者中出现异常表达。结论:血清miR-200a极大程度地参与了肝癌发生,对肝硬化及肝癌具有一定的诊断价值。