Development of lactate-related gene signature and prediction of overall survival and chemosensitivity in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor of the digestive system that contains high levels of immune cells. Lactic acid, a major metabolite, plays a crucial role in tumor development, maintenance, and therapeutic response. However, the prognostic potential and therapeutic biomarker potential of lactate-related genes (LRGs) in CRC patients remain to be elucidated. METHODS: We collected the mRNA expression profile and clinical data of CRC patients from the Cancer Genome Atlas (TCGA) database and the GSE59382 cohort. Univariate Cox regression, Lasso regression and multivariate Cox regression analysis were used to construct the prognosis model. Combined with the risk score and important clinicopathological features, the nomogram was established. In addition, the relationship between risk score and immune infiltration, immune checkpoint gene expression, and drug sensitivity was investigated. RESULTS: We constructed lactate-related gene signatures (LRGS) based on four LRGs, which independently predicted the prognosis of CRC. Patients with different risk scores are found to have distinct immune status, tumor mutation load, immune response, and drug sensitivity. In addition, nomogram results determined by risk scores and clinical factors have higher predictive performance. CONCLUSION: We found that LRGS is a reliable biomarker for predicting clinical outcomes, evaluating immune infiltration and efficacy, and predicting the sensitivity to drugs in patients with CRC.

Mitochondrial aggregation caused by cytochalasin B compromises the efficiency and safety of three-parent embryo.

It is widely accepted that cytochalasin B (CB) is required in enucleation of the oocyte in order to stabilize the cytoplasm. However, CB treatment results in the uneven distribution of mitochondria, with aggregation towards the nucleus, which might compromise the efficiency and safety of a three-parent embryo. Here, we demonstrated that CB treatment affected mitochondrial dynamics, spindle morphology and mitochondrial DNA carryover in a concentration-dependent manner. Our results showed that mouse oocytes treated with over 1 µg/ml CB exhibited a more aggregated pattern of mitochondria and diminished filamentous actin expression. Abnormal fission of mitochondria together with changes in spindle morphology increased as CB concentration escalated. Based on the results of mouse experiments, we further revealed the practical value of these findings in human oocytes. Chip-based digital PCR and pyrosequencing revealed that the mitochondrial carryover in reconstituted human embryos was significantly reduced by modifying the concentration of CB from the standard 5 µg/ml to 1 µg/ml before spindle transfer and pronuclear transfer. In conclusion, our findings provide an optimal manipulation for improving the efficiency and safety of mitochondrial replacement therapy.

MicroRNAs in regulation of pluripotency and somatic cell reprogramming: small molecule with big impact.

MicroRNAs (miRNAs), a group of small non-coding RNAs, have emerged as significant modulators in the establishment and generation of pluripotency, a developmental process that consists of complex cell-fate arrangements. The finding of embryonic stem cell (ESC) cycle-specific miRNAs reveals an important regulation scheme of pluripotency. Subsequent studies showed the ESC-enriched or ESC-depleted miRNAs can regulate induced pluripotent stem cells(iPSC). Moreover, miRNA profiling of iPSC and ESC may distinguish them from one another and facilitate the complex of regulatory network. The accumulative effects of miRNA action enable using miRNA alone to generate iPSCs. Despite the robustness of iPSC studies, further investigations are needed since miRNA may have more impact on induced pluripotency, and the roles of miRNAs in somatic cell nuclear transfer (SCNT), another approach toward cellular reprogramming, remains unclear. This point-of-view article will discuss miRNAs and their impact on the normal and induced pluripotency, as well as bring new insights on somatic cell reprogramming.