LncRNA TUG1 inhibits neuronal apoptosis in status epilepticus rats via targeting the miR-421/mTOR axis.

Status epilepticus (SE) induces apoptosis of hippocampal neurons. However, the underlying mechanism in SE is not fully understood. Recently, lncRNA TUG1 is reported as a significant mediator in neuronal development. In present study, we aimed to investigate whether lncRNA TUG1 induces apoptosis of hippocampal neurons in SE rat models. TUG1 expression in serum of normal volunteers and SE patients, SE rats and neurons with epileptiform discharge was detected. SE rat model was established and intervened with TUG1 to evaluate hippocampal neuronal apoptosis. The experiments in vitro were further performed in neurons with epileptiform discharge to verify the effects of TUG1 on neuronal apoptosis of SE rats. The downstream mechanism of TUG1 was predicted and verified. miR-421 was intervened to perform the rescue experiments. Levels of oxidative stress and inflammation-related factors and mTOR pathway-related proteins in SE rats and hippocampal neurons were detected. TUG1 was highly expressed in serum of SE patients, SE rats and neurons with epileptiform discharge. Inhibition of TUG1 relieved pathological injury, oxidative stress and inflammation and reduced neuronal apoptosis in SE rats, which were further verified in hippocampal neurons. TUG1 upregulated TIMP2 expression by targeting miR-421. Overexpressed miR-421 inhibited hippocampal neuronal apoptosis. TUG1 knockout inactivated the mTOR pathway via the miR-421/TIMP2 axis to relieve neuronal apoptosis, oxidative stress and inflammation in SE rats and hippocampal neurons. Taken together, these findings showed that downregulation of lncRNA TUG1 inhibited apoptosis of hippocampal neurons in SE rats, and attenuated oxidative stress and inflammation damage through regulating the miR-421/mTOR axis.

Association of Polymorphisms of Mismatch Repair Genes hMLHI and hMSH2 with Breast Cancer Susceptibility: A Meta-Analysis.

This article serves to evaluate the association of polymorphisms of mismatch repair genes (hMLH1 and hMSH2) with breast cancer (BC) susceptibility through a meta-analysis. Our methods involved extensive research in Chinese and English databases that examined the association of hMLH1 and hMSH2 polymorphisms with susceptibility to BC, strictly abiding by established inclusion and exclusion criteria. Software Stata 12.0 was used for statistical data analysis. A total of 12 studies were available for meta-analysis, published between 2014 and 2017, of which respectively 9 studies explored the association of hMLH1 (rs1799977 A > G and rs63750447 T > A) and 3 studies explored the association of hMSH2 (rs4987188 [Gly322Asp] and rs17217772 [Asn127Ser]) with patients' susceptibility to BC. The results showed that both the rs1799977 A > G polymorphism GA + GG genotype (especially in the Caucasian population) and the rs63750447 T > A polymorphism TA + AA genotype in the hMLH1 gene increased patients' susceptibility to BC. The genotype detection method was selected as a target for subgroup analysis. According to studies where MassARRAY assay was conducted, the rs1799977 A > G polymorphism was correlated with BC susceptibility in the dominant model, while rs4987188 (Gly322Asp) and rs17217772 (Asn127Ser) of the hMSH2 gene presented no observable correlation with the risk for BC. Both the rs1799977 A > G and rs63750447 T > A polymorphisms in the hMLH1 gene showed a significant association with a markedly increased risk for BC, while rs4987188 (Gly322Asp) and rs17217772 (Asn127Ser) of the hMSH2 gene were not clearly correlated with BC susceptibility.