MiR-7 inhibits progression of hepatocarcinoma by targeting KLF-4 and promises a novel diagnostic biomarker.

BACKGROUND: MicroRNAs are 22-24 nt non-coding RNAs that bind to the 3' UTR of target mRNAs, thereby inducing mRNA degradation or inhibiting mRNA translation. Due to their implication in the regulation of post-transcriptional processes, the role of miRNAs in hepatocellular carcinoma (HCC) has been extensively studied. However, the function of miR-7 in HCC remains to be demonstrated. METHODS: 50 paired HCC tissues and matched peritumor tissues from patients were collected. The mRNA level of miR-7 was detected by qRT-PCR. The protein level of Kruppel-like factor 4 (KLF-4) was determined by western blot. Cell proliferation and invasive ability were measured using MTT and transwell invasion assay, respectively. RESULTS: We demonstrated that miR-7 was downregulated in 50 HCC tissues and the low expression of miR-7 was significantly correlate with tumour size. Moreover, overexpression of miR-7 significantly inhibited the proliferation and invasion of HCC cells. Over 100 target genes of miR-7 were predicted by Targetscan, and KLF-4 was indicated as the most promising candidate. Luciferase report assay showed that KLF-4 could be silenced by miR-7, so as to restore the impairment of cell proliferation and invasion in HCC cells. CONCLUSIONS: In summary, we revealed a role of miR-7-KLF-4 axis in HCC cells, and the combination of both biomarkers might improve HCC diagnosis.

Stress Hormone Cortisol Enhances Bcl2 Like-12 Expression to Inhibit p53 in Hepatocellular Carcinoma Cells.

BACKGROUND AND AIMS: The pathogenesis of hepatocellular carcinoma (HC) is unclear. It is suggested that psychological stress associates with the pathogenesis of liver cancer. Bcl2-like protein 12 (Bcl2L12) suppresses p53 protein. This study tests a hypothesis that the major stress hormone, cortisol, inhibits the expression of p53 in HC cells (HCC) via up regulating the expression of Bcl2L12. METHODS: Peripheral blood samples were collected from patients with HC to be analyzed for the levels of cortisol. HCC were cultured to assess the role of cortisol in the regulation of the expression of Bcl2L12 and p53 in HCC. RESULTS: We observed that the serum cortisol levels were higher in HC patients. Expression of Bcl2L12 in HCC was correlated with serum cortisol. Cortisol enhanced the Bcl2L12 expression in HCC. Bcl2L12 binding to the TP53 promoter was correlated with p53 expression in HCC. Cortisol increased the Bcl2L12 expression in HCC to inhibit p53 expression. CONCLUSIONS: Stress hormone cortisol suppresses p53 in HCC via enhancing Bcl2L12 expression in HCC. The results suggest that cortisol may be a therapeutic target for the treatment of HC.

Identification of potential prognostic biomarkers among gene models for coiled-coil domain-containing family members in hepatocellular carcinoma elucidates their influence on the hypoxia pathway and immune microenvironment.

Background: The family of coiled-coil domain-containing (CCDC) proteins participates in a wide range of physiological functions and plays a pivotal role in governing the invasion and metastasis of malignant tumor cells. Nonetheless, the precise mechanism governing the interaction among the immune microenvironment, hypoxia pathway, and proliferation in hepatocellular carcinoma (HCC) remains elusive. In this study, our objective was to identify the prognostic significance of CCDC family genes in HCC. Methods: We conducted an analysis of RNA-seq data from HCC patients sourced from The Cancer Genome Atlas (TCGA) database. Our analysis involved comparing the expression profiles of 168 CCDC family genes between tumor and normal tissues to identify differentially expressed genes (DEGs). The prognostic value of these genes was verified using overall survival (OS) data from TCGA-LIHC patients, employing Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. Subsequently, we constructed a prognostic signature known as the CCDC score and validated it using additional datasets (ICGC-LIRI-JP and GSE14520). Additionally, we performed functional enrichment analysis and conducted an assessment of the tumor immune microenvironment (TIME). Results: We identified 34 DEGs of the CCDC family. Among them, six DEGs (CCDC6/22/51/59/132/134) were upregulated and associated with poor prognosis. Higher CCDC score was an independent predictor of poor OS in TCGA-HCC patients (P<0.001, HR =2.37), which was validated in the ICGC-LIRI-JP (P=0.021, HR =2.15) and GSE14520 (P=0.002, HR =2.23) datasets. Functional enrichment analysis showed that hypoxia pathway genes were enriched in the high CCDC score group. Furthermore, immune microenvironment analysis demonstrated that high CCDC score was associated with a suppressed TIME caused by the extrinsic immune escape. Conclusions: The CCDC score, derived from six CCDC genes, exhibits remarkable expression levels in liver cancer and holds promise as an independent prognostic indicator. Our bioinformatics analysis revealed a high CCDC score is strongly associated with activation of the hypoxia pathway and an immunosuppressive tumor microenvironment in HCC. This profound finding may serve as a cornerstone for innovative targeted drug therapies and pave the way for further investigations into the underlying mechanisms of CCDC-related carcinogenesis in liver cancer.

Bee venom protects against pancreatic cancer via inducing cell cycle arrest and apoptosis with suppression of cell migration.

Background: Pancreatic cancer seriously threatens human health. Bee venom is a mixture of enzymes, peptides, and amines. Due to its biological activity, bee venom is widely used as an anti-inflammatory agent and pain reliever. However, little is known about the effect of bee venom on pancreatic cancer. Methods: Firstly, the Cell Counting Kit-8 (CCK-8) assay was conducted to analyze the cytotoxicity of bee venom on PANC-1 and AsPC-1 cells. Then, we evaluated the cell cycle and apoptosis by flow cytometry and the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. In addition, cell migration was analyzed by the cell scratch test and Transwell assay. Western blot was performed to assess the expression of proteins involved in the regulation of cell cycle arrest and apoptosis. Results: Results demonstrated that bee venom significantly suppressed cell proliferation via inducing cell cycle arrest and apoptosis with suppression of cell migration. Bee venom induced S phase arrest and ameliorated the protein expression of cyclins and cyclin-dependent kinases (CDKs). At the same time, bee venom can activate the p53-p21 pathway. Experimental data also showed that bee venom induced cell apoptosis and impeded cell migration. Conclusions: The present study revealed that bee venom could effectively inhibit tumor progression in pancreatic cancer cells, indicating the possibility of bee venom as an anti-tumor drug in pancreatic cancer.