Potential HNF1A-AS1/miR-214/INHBA signal regulation mechanism in colorectal cancer based on bioinformatics analysis and validation

Preceding studies have identified that noncoding RNA plays a significant role in the occurrence and development of tumors. Colorectal cancer (CRC) has attracted increasing attention due to its high incidence and mortality rate. Based on Cancer Genome Atlas (TCGA) database analysis, it was found that compared with normal tissues, HNF1A-AS1 and INHBA were highly expressed in CRC tissues; miR-214 was relatively low expressed, and it is predicted to specifically target the3' untranslated region (3'UTR region) of INHBA. Besides, the result was consistent with the quantitative reverse transcription PCR (RT-qPCR) verification results of 17 CRC cases and adjacent tissues collected clinically. Western Blot (WB) manifested that INHBA protein was highly expressed in CRC tissues, which was consistent with the results of CRC cell lines (HT29, SW480). Immunohistochemical (IHC) staining demonstrated that INHBA protein was brownish yellow, overwhelming majority of INHBA protein were located in the cytoplasm, and expression level was significantly higher than that in adjacent tissues. Based on previous studies, the biological process of INHBA-mediated TGF-β/Smad signaling pathway inducing the proliferation and invasion of CRC has been partially confirmed, but the upstream signaling molecules and mechanisms which regulating INHBA remain unclear. Herein, benefiting from bioinformatics, preliminary experimental results and previous research, they provide basis for the follow-up study on the regulation of HNF1A-AS1/miR-214/INHBA signal axis in CRC.

Erythroid Differentiation Regulator 1 Strengthens TCR Signaling by Enhancing PLCγ1 Signal Transduction Pathway

Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca2+/NFAT1 signal transduction pathway.

Enhanced loss of retinoic acid network genes in Xenopus laevis achieves a tighter signal regulation

Retinoic acid (RA) is a major regulatory signal during embryogenesis produced from vitamin A (retinol) by an extensive, autoregulating metabolic and signaling network to prevent fluctuations that result in developmental malformations. Xenopus laevis is an allotetraploid hybrid frog species whose genome includes L (long) and S (short) chromosomes from the originating species. Evolutionarily, the X. laevis subgenomes have been losing either L or S homoeologs in about 43% of genes to generate singletons. In the RA network, out of the 47 genes, about 46% have lost one of the homoeologs, like the genome average. In contrast, RA metabolism genes from storage (retinyl esters) to retinaldehyde production exhibit enhanced gene loss with 75% singletons out of 28 genes. The effect of this gene loss on RA signaling autoregulation was studied. Employing transient RA manipulations, homoeolog gene pairs were identified in which one homeolog exhibits enhanced responses or looser regulation than the other, while in other pairs both homoeologs exhibit similar RA responses. CRISPR/Cas9 targeting of individual homoeologs to reduce their activity supports the hypothesis where the RA metabolic network gene loss results in tighter network regulation and more efficient RA robustness responses to overcome complex regulation conditions.

Cellular and Molecular Mechanism of Traditional Chinese Medicine on Ventricular Remodeling

Ventricular remodeling is related to the renin-angiotensin-aldosterone system, immune system, and various cytokines involved in inflammation, apoptosis, and cell signal regulation. Accumulated studies have shown that traditional Chinese medicine can significantly inhibit the process of ventricular remodeling, which may be related to the mechanism mentioned above. Here, we conducted a system overview to critically review the cellular and molecular mechanism of traditional Chinese medicine on ventricular remodeling. We mainly searched PubMed for basic research about the anti-ventricular remodeling of traditional Chinese medicine in 5 recent years, and then objectively summarized these researches. We included more than 25 kinds of Chinese herbal medicines including Qi-Li-Qian-Xin, Qi-Shen-Yi-Qi Pill, Xin-Ji-Er-Kang Formula, and Yi-Qi-Wen-Yang Decoction, and found that they can inhibit ventricular remodeling effectively through multi-components and multi-action targets, which are promoting the clinical application of traditional Chinese medicine.

Construction of protocell-based artificial signal transduction pathway

The maintenance of an orderly and controllable multicellular society depends on the communication and signal regulation among various types of biological cells. How to replicate complicate signal transduction pathways in...