Yanping Li

Background: Pancreatic cancer is a highly aggressive tumor with a poor prognosis due to challenging early diagnosis and limited treatment options. CHEK1, a crucial cell cycle regulator, is important in tumor development, but its role in pancreatic cancer remains under-researched in terms of expression, function, and regulation. Objective: To study the effect of CHEK1 on proliferation, migration and cell cycle of pancreatic cancer, and to construct a prognostic prediction model to investigate the effect of CHEK1 on the prognosis of pancreatic cancer. Methods: We conducted a systematic investigation into the expression characteristics and biological functions of CHEK1 in pancreatic cancer, utilizing an integration of bioinformatics analyses and in vitro experiments. Initially, we performed an in-depth analysis of CHEK1 expression profiles and their clinical significance in pancreatic cancer, drawing on data from several public databases, including UALCAN, TNMplot, and TISIDB. Subsequently, we validated the impact of CHEK1 on the malignant biological behaviors of pancreatic cancer cells, specifically focusing on proliferation and migration, through a series of in vitro cellular experiments. Results: The findings revealed that CHEK1 expression levels were significantly upregulated in pancreatic cancer tissues, which correlated positively with tumor pathological grade. KEGG pathway enrichment analysis further indicated that CHEK1 exerts critical regulatory functions across multiple oncogenic pathways, including cellular proliferation, G2/M checkpoint control, DNA replication, and DNA damage repair. In vitro experimental demonstrated that CHEK1 overexpression substantially increased both the proliferative progression and migratory capacity of pancreatic cancer cells. Conclusions: Our study indicates that high CHEK1 expression could be an independent prognostic marker for pancreatic cancer and may drive cancer progression by influencing DNA replication and G2/M checkpoint pathways. These insights offer a foundation for future research and targeted precision therapy involving CHEK1.

Ovarian cancer is of the most lethal malignancy and causes serious threat to women health worldwide. A deep understanding of molecular mechanisms underlying ovarian cancer progression is critical for the development of promising therapeutic strategies. In this study, we aimed to employ immunohistochemistry to determine the protein level of HDAC7 in patient tissues, our data showed HDAC7 levels are upregulated in tumour tissues. In addition, we also performed Kaplan–Meier survival analysis to investigate the association between HDAC7 expression and clinical prognosis, and found that HDAC7 expression was associated with poor prognosis in ovarian cancer patients. Inhibition of HDAC7 cells resulted in lower cell proliferation, invasion and colony formation. Furthermore, we also found that HDAC7 inhibition suppressed PI3K/AKT/mTOR pathway. In contrast, exogenous HDAC7 expression activated the PI3K/AKT/mTOR pathway in HDAC7 knockout cells and rescued the cell proliferation, invasion and colony formation. However, inhibition of p‐AKT induced lower cell proliferation, metastasis and colony formation abilities. In murine model, HDAC7 KO significantly decreased the tumour burden. These data indicate that HDAC7 is involved in regulation of PI3K/AKT/mTOR pathway and targeting of HDAC7 could be potential therapeutic strategy in the treatment of ovarian cancer.

Background: Copper chaperone for superoxide dismutase ( CCS) is an essential component of the oxidation-reduction system. In breast cancer cells, CCS expression is highly up-regulated, which contributes to cellular proliferation and migration. Breast cancer is a multifaceted disease with different tumor prognoses and responses to clinical treatments, which may be associated with multiple molecular subtypes of CCS. Methods: The CCS expression patterns in breast cancer were investigated by TNMplot, cBioPortal, and HPA network database. The correlation of CCS expression with clinicopathological parameters was analyzed using the UALCAN database. The Cancer Genome Atlas (TCGA) data set was used to analyze the Clinical characteristics of CCS in luminal B patients. The bc-GenExMiner database was used to analyze the effects of BReast-CAncer susceptibility gene (BRCA)1/2, TP53 mutation status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER) expression on CCS expression. The survival curves and prognostic value of CCS in luminal B breast cancer were performed through Kaplan-Meier curves, univariate and multivariate Cox regression using the PrognoScan, bc-GenExMiner, and Clinical bioinformatics analysis platform. Results: We found that CCS expression was associated with patient age, race, ER, and PR status. We also discovered that BRCA1/2 mutations had an effect on CCS expression. The luminal B subtype had the highest CCS expression, which was linked to poor survival compared with other subtypes. In addition, Kaplan-Meier curve analysis showed that luminal B patients with high CCS mRNA expression showed a poor survival and the CCS gene is an independent predictor of outcome in patients with luminal B breast cancer by univariate and multivariate Cox regression. Conclusions: Our findings emphasize the significant expression of CCS in luminal B breast cancer and its potential as an autonomous prognostic determinant for this specific molecular subtype. These findings suggest that CCS holds promise as a prospective marker for the treatment of luminal B breast cancer.

It was proven that PGK1 plays a vital role in the proliferation, migration, and invasion of human breast cancer. However, the correlation of PGK1 mRNA and protein expression with clinicopathologic characteristics and prognostic values according to various kinds of breast cancer patient classifications remains unsufficient. Here, we analyzed data from the Oncomine database, Breast cancer Gene-Expression Miner v4.5, TNMplot, MuTarget, PrognoScan database, and clinical bioinformatics to investigate PGK1 expression distribution and prognostic value in breast cancer patients. Our study revealed that the mRNA and protein expression levels of PGK1 were up-regulated in various clinicopathologic types of breast cancer. Moreover, the expression of PGK1 was correlated with mutations of common tumor suppressor genes TP53 and CDH1. In addition, we found that high mRNA level of PGK1 was significantly associated with poor OS, RFS, and DMFS. Notably, Cox regression analysis showed that PGK1 could be used as an independent prognostic marker. In summary, the aforementioned findings suggested that PGK1 might be not only explored as a potential biomarker, but also combined with TP53/CDH1 for chemotherapy in breast cancer.

Porcine circovirus type 2 (PCV2) is the primary cause of post-weaning multisystemic wasting syndrome (PMWS) and other PCV-associated diseases. According to our previous RNA-sequencing analysis, the differences in the susceptibility to PCV2 infection depended on the genetic differences between the Laiwu (LW) and Yorkshire × Landrace crossbred (YL) pigs, but the cellular microRNA (miRNA) that are differentially expressed between the LW and YL pigs before and after PCV2 infection remain to be determined. In this study, high-throughput sequencing was performed to determine the abundance and differential expression of miRNA in lung tissues from PCV2-infected and PCV2-uninfected LW and YL pigs. In total, 295 known and 95 novel miRNA were identified, and 23 known and 25 novel miRNA were significantly differentially expressed in the PCV2-infected vs. PCV2-uninfected LW pigs and/or the PCV2-infected vs. PCV2-uninfected YL pigs. The expression levels of ssc-miR-122, ssc-miR-192, ssc-miR-451, ssc-miR-486, and ssc-miR-504 were confirmed by quantitative real-time PCR (qRT-PCR). Analysis of the potential targets of the four up-regulated miRNA (i.e., ssc-miR-122, ssc-miR-192, ssc-miR-451 and ssc-miR-486) identified pathways and genes that may be important for disease resistance. Among the up-regulated miRNA, ssc-miR-122 can repress the protein expression and viral DNA replication of PCV2 and down-regulate the expression of the nuclear factor of activated T-cells 5 (NFAT5) and aminopeptidase puromycin sensitive (NPEPPS) by binding to their 3′ untranslated region (3′UTR) in PK15 cells. Therefore, ssc-miR-122 may indirectly suppress PCV2 infection by targeting genes related to the host immune system, such as NFAT5 and NPEPPS.