Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues.

dGlucose confers acid resistance on exponentially growing bacteria by repressing formation of the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and consequently activating acid resistance genes. Therefore, in a glucose-rich growth environment, bacteria are capable of resisting acidic stresses due to low levels of cAMP-CRP. Here we reveal a second mechanism for glucose-conferred acid resistance. We show that glucose induces acid resistance in exponentially growing bacteria through pyruvate, the glycolysis product. Pyruvate and/or the downstream metabolites induce expression of the small noncoding RNA (sncRNA) Spot42, and the sncRNA, in turn, activates expression of the master regulator of acid resistance, RpoS. In contrast to glucose, pyruvate has little effect on levels of the cAMP-CRP complex and does not require the complex for its effects on acid resistance. Another important difference between glucose and pyruvate is that pyruvate can be produced by bacteria. This means that bacteria have the potential to protect themselves from acidic stresses by controlling glucose-derived generation of pyruvate, pyruvate-acetate efflux, or reversion from acetate to pyruvate. We tested this possibility by shutting down pyruvate-acetate efflux and found that the resulting accumulation of pyruvate elevated acid resistance. Many sugars can be broken into glucose, and the subsequent glycolysis generates pyruvate. Therefore, pyruvate-associated acid resistance is not confined to glucose-grown bacteria but is functional in bacteria grown on various sugars. G astric acid (pH 2) in the stomach of the host efficiently kills or inhibits the growth of bacterial pathogens. After being swallowed, enteric organisms have to overcome the low pH of gastric acid. Acidic stresses also come from bacterial growth per se. It is well established that bacteria such as Escherichia coli utilize the phosphotransacetylase (Pta)-acetate kinase (AckA) pathway to generate ATP from acetate production in glucose-containing environments even in the presence of ample oxygen (1). The phenomenon of overflow metabolism has been attributed to an imbalance between the fluxes of glucose uptake and those for energy production and biosynthesis (2), probably caused by improperly controlled glucose uptake and/or limited activity of the tricarboxylic acid (TCA) cycle (3). As a weak acid, acetate is toxic to bacteria and has been found to uncouple the transmembrane pH gradient (4, 5), acidify the cytoplasm, and interfere with methionine biosynthesis (6-8). Therefore, acid resistance (AR) is an important ability that E. coli possesses to survive low pH and flourish. Indeed, E. coli organisms can be so resistant to low pH that they survive gastric acid, colonize the gut, and cause diseases even though small numbers of them (10 to 100) are ingested (9, 10).The cyclic AMP (cAMP) receptor protein (CRP) is a crucial regulator of AR in E. coli. It has been demonstrated that CRP negatively regulates AR by repressing a set of AR genes (11,12). CRP has to form a complex ...

Several epidemiological studies have reported that polymorphisms in microRNA-196a2 (miR-196a2) were associated with various cancers. However, the results remained unverified and were inconsistent in different cancers. Therefore, we carried out an updated meta-analysis to elaborate the effects of rs11614913 polymorphism on cancer susceptibility. A total of 84 articles with 35,802 cases and 41,541 controls were included to evaluate the association between the miR-196a2 rs11614913 and cancer risk by pooled odds ratios (ORs) and 95% confidence intervals (CIs). The results showed that miR-196a2 rs11614913 polymorphism is associated with cancer susceptibility, especially in lung cancer (homozygote comparison, OR =0.840, 95% CI =0.734–0.961; recessive model, OR =0.858, 95% CI =0.771–0.955), hepatocellular carcinoma (allelic contrast, OR =0.894, 95% CI =0.800–0.998; homozygote comparison, OR =0.900, 95% CI =0.813–0.997; recessive model, OR =0.800, 95% CI =0.678–0.944), and head and neck cancer (allelic contrast, OR =1.076, 95% CI =1.006–1.152; homozygote comparison, OR =1.214, 95% CI =1.043–1.413). In addition, significant association was found among Asian populations (allele model, OR =0.847, 95% CI =0.899–0.997, P=0.038; homozygote model, OR =0.878, 95% CI =0.788–0.977, P=0.017; recessive model, OR =0.895, 95% CI =0.824–0.972, P=0.008) but not in Caucasians. The updated meta-analysis confirmed the previous results that miR-196a2 rs11614913 polymorphism may serve as a risk factor for patients with cancers.

The current study is to investigate the expression pattern and biological function of long non-coding RNA Focally gastric cancer-associated transcript3 (GACAT3) in bladder cancer. Real-time quantitative qPCR was used to detect the expression level of GACAT-3 in tumor tissues and paired normal tissues. Human bladder cancer T24 and 5637 cell lines were transiently transfected with specific CRISPR-Cas13 or negative control CRISPR-Cas13. Cell migration, proliferation, and apoptosis were measured by using wound healing assay CCK-8 assay and Caspase-3 ELISA assay, respectively. The expression changes of p21, Bax, and E-cadherin after knockdown of GACAT3 were detected by using Western blot. The results demonstrated that GACAT3 was up-regulated in bladder cancer tissues than that in the paired normal tissues. Inhibition of cell proliferation, increased apoptosis, and decreased motility were observed in T24 and 5637 cell lines transfected by CRISPR-Cas13 targeting GACAT3. Downregulation of GACAT3 increased p21, Bax, and E-cadherin expression and silencing these genes could eliminate the phenotypic changes induced by knockdown of GACAT3. A ceRNA mechanism for GACAT3 was also revealed. By using CRISPR-Cas13 biotechnology, we suggested that GACAT3 may be a novel target for diagnosis and treatment of bladder cancer.