Various studies have shown that lysine acetyltransferase 2A (KAT2A), E2F transcription factor 1 (E2F1), and ubiquitin conjugating enzyme E2 C (UBE2C) genes regulated the proliferation and migration of tumor cells through regulating the cell cycle. However, there is a lack of in-depth and systematic research on their mechanisms of action. This study analyzed The Cancer Genome Atlas (TCGA) to screen potential candidate genes and the regulation network of KAT2A and E2F1 complex in pan-cancer. Quantitative real-time PCR (qRT-PCR) and Western blotting (WB), cell phenotype detection, immunofluorescence co-localization, chromatin immunoprecipitation assay (ChIP), and RNA-Seq techniques were used to explore the functional of a candidate gene, UBE2C. We found that the expression of these three genes was significantly higher in more than 10 tumor types compared to normal tissue. Moreover, UBE2C was mainly expressed in tumor cells, which highlighted the impacts of UBE2C as a specific therapeutic strategy. Moreover, KAT2A and E2F1 could promote cell proliferation and the migration of cancer cells by enhancing the expression of UBE2C. Mechanically, KAT2A was found to cooperate with E2F1 and be recruited by E2F1 to the UBE2C promoter for elevating the expression of UBE2C by increasing the acetylation level of H3K9.

Physical activity exerts positive effects on glycemic control in type 2 diabetes (T2D), which is mediated in part by extensive metabolic and molecular remodeling of skeletal muscle in response to exercise, while many regulators of skeletal muscle remain unclear. In the present study, we investigated the effects of acute exercise on skeletal muscle transcriptomic responses in the Goto-Kakizaki (GK) rats which can spontaneously develop T2D. The transcriptomes of skeletal muscle from both 8-week-old GK and Wistar rats that underwent a single exercise session (60 min running using an animal treadmill at 15 m/min) or remained sedentary were analyzed by next-generation RNA sequencing. We identified 819 differentially expressed genes in the sedentary GK rats compared with those of the sedentary Wistar rats. After a single bout of running, we found 291 and 598 genes that were differentially expressed in the exercise GK and exercise Wistar rats when compared with the corresponding sedentary rats. By integrating our data and previous studies including RNA or protein expression patterns and transgenic experiments, the downregulated expression of Fasn and upregulated expression of Tbc1d1, Hk2, Lpin1, Ppargc1a, Sorbs1, and Hmox1 might enhance glucose uptake or improve insulin sensitivity to ameliorate hyperglycemia in the exercise GK rats. Our results provide mechanistic insight into the beneficial effects of exercise on hyperglycemia and insulin action in skeletal muscle of diabetic GK rats.

Skeletal muscle long non-coding RNAs (lncRNAs) were reported to be involved in the development of type 2 diabetes (T2D). However, little is known about the mechanism of skeletal muscle lncRNAs on hyperglycemia of diabetic Goto-Kakizaki (GK) rats at the age of 3 and 4 weeks. To elucidate this, we used RNA-sequencing to profile the skeletal muscle transcriptomes including lncRNAs and mRNAs, in diabetic GK and control Wistar rats at the age of 3 and 4 weeks. In total, there were 438 differentially expressed mRNAs (DEGs) and 401 differentially expressed lncRNAs (DELs) in skeletal muscle of 3-week-old GK rats compared with age-matched Wistar rats, and 1000 DEGs and 726 DELs between GK rats and Wistar rats at 4 weeks of age. The protein–protein interaction analysis of overlapping DEGs between 3 and 4 weeks, the correlation analysis of DELs and DEGs, as well as the prediction of target DEGs of DELs showed that these DEGs (Pdk4, Stc2, Il15, Fbxw7 and Ucp3) might play key roles in hyperglycemia, glucose intolerance, and increased fatty acid oxidation. Considering the corresponding co-expressed DELs with high correlation coefficients or targeted DELs of these DEGs, our study indicated that these dysregulated lncRNA-mRNA pairs (NONRATG017315.2-Pdk4, NONRATG003318.2-Stc2, NONRATG011882.2-Il15, NONRATG013497.2-Fbxw7, MSTRG.1662-Ucp3) might be related to above biological processes in GK rats at the age of 3 and 4 weeks. Our study could provide more comprehensive knowledge of mRNAs and lncRNAs in skeletal muscle of GK rats at 3 and 4 weeks of age. And our study may provide deeper understanding of the underlying mechanism in T2D of GK rats at the age of 3 and 4 weeks.

DNA damage repair (DDR) is critical in maintaining normal cellular function and genome integrity and is associated with cancer risk, progression, and therapeutic response. However, there is still a lack of a thorough understanding of the effects of DDR genes’ expression level in cancer progression and therapeutic resistance. Therefore, we defined a tumor-related DDR score (TR-DDR score), utilizing the expression levels of 20 genes, to quantify the tumor signature of DNA damage repair pathways in tumors and explore the possible function and mechanism for the score among different cancers. The TR-DDR score has remarkably predictive power for tumor tissues. It is a more accurate indicator for the response of chemotherapy or immunotherapy combined with the tumor-infiltrating lymphocyte (TIL) and G2M checkpoint score than the pre-existing predictors (CD8 or PD-L1). This study points out that the TR-DDR score generally has positive correlations with patients of advanced-stage, genome-instability, and cell proliferation signature, while negative correlations with inflammatory response, apoptosis, and p53 pathway signature. In the context of tumor immune response, the TR-DDR score strongly positively correlates with the number of T cells (CD4+ activated memory cells, CD8+ cells, T regs, Tfh) and macrophages M1 polarization. In addition, by difference analysis and correlation analysis, COL2A1, MAGEA4, FCRL4, and ZIC1 are screened out as the potential modulating factors for the TR-DDR score. In summary, we light on a new biomarker for DNA damage repair pathways and explore its possible mechanism to guide therapeutic strategies and drug response prediction.

The development of high-throughput omics technology has greatly promoted the development of biomedicine. However, the poor reproducibility of omics techniques limits their application. It is necessary to use standard reference materials of complex RNAs or proteins to test and calibrate the accuracy and reproducibility of omics workflows. The transcriptome and proteome of most cell lines shift during culturing, which limits their applicability as standard samples. In this study, we demonstrated that the human hepatocellular cell line MHCC97H has a very stable transcriptome (r = 0.983~0.997) and proteome (r = 0.966~0.988 for data-dependent acquisition, r = 0.970~0.994 for data-independent acquisition) after 9 subculturing generations, which allows this steady standard sample to be consistently produced on an industrial scale in long term. Moreover, this stability was maintained across labs and platforms. In sum, our study provides omics standard reference material and reference datasets for transcriptomic and proteomics research. This helps to further standardize the workflow and data quality of omics techniques and thus promotes the application of omics technology in precision medicine.