A pan-cancer analysis of the expression and prognostic significance of PDRG1.

Background: PDRG1 are involved in various physiological regulations of cells, include cell proliferation, growth, apoptosis and cell cycle regulation, but their roles in cancer have not been clearly studied. Methods: Firstly, we evaluated the expression and prognostic significance of PDRG1 using a pan-cancer analysis of The Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression (GTEx) databases. Secondly, correlations between PDRG1 and pan-cancer immune cells, m6A methylation, tumor mutation burden (TMB), and microsatellite instability (MSI) were investigated. Finally, we explored the relationship between PDRG1 expression and clinical stage in hepatocellular carcinoma (HCC). Results: We found that PDRG1 was significantly overexpressed in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), liver hepatocellular carcinoma (LIHC), and other tumor tissues and was associated with prognosis. In addition, PDRG1 was closely associated with pan-cancer immune cells, m6A methylation, TMB, and MSI expression. The expression of PDRG1 in HCC was correlated with clinical stage, and western blot assay confirmed that PDRG1 was significantly overexpressed in HCC tissues. Conclusions: PDRG1 may be an important pan-cancer molecular biomarker for diagnosis and prognosis, and our results may provide a theoretical basis for its future clinical application in cancer diagnosis, treatment, and prognosis, and have been preliminarily validated in HCC.

Efficacy and safety of gemcitabine-capecitabine combination therapy for pancreatic cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients. Here, we conducted a meta-analysis to compare the efficacy and safety of gemcitabine (Gem) with GemCap for pancreatic cancer. METHODS: The database of MEDLINE (PubMed), EMBASE, Cochrane Central Controster of Controlled Trials, Web of Science was searched for relevant randomized controlled trials before 8 April, 2020. The outcomes were overall survival (OS), 12-month survival rate, progress free survival (PFS), partial response rate (PRR), objective response rate (ORR), and Grade 3/4 toxicities. RESULTS: Five randomized controlled trials involving 1879 patients were included in this study. The results showed that GemCap significantly improves the OS (hazard ratio = 1.15, 95% CI: 1.037-1.276, P = .008), PFS (hazard ratio = 1.211, 95% CI 1.09-1.344, P = 0), PRR (relative risk (RR) = 0.649, 95% CI 0.488-0.862, P = .003), ORR (RR = 0.605, 95% CI 0.458-0.799, P = 0), and the overall toxicity (RR = 0.708, 95% CI 0.620-0.808, P = .000) compared to Gem alone. However, no significant difference was found in 12-month survival. CONCLUSIONS: Despite a higher incidence of Grade 3/4 toxicity, GemCap was associated with better outcomes of OS, PFS, PRR, ORR, as compared with Gem, which is likely to become a promising therapy for pancreatic cancer.

LINC00339 promotes cell proliferation and metastasis in pancreatic cancer via miR-497-5p/IGF1R axis.

PURPOSE: To investigate the role and mechanism of long non-coding (lnc) RNA LINC00339 in pancreatic cancer (PANC), and provided a potential target for its biological diagnosis and treatment. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00339 in PANC tissue specimens and cell lines. The experimental cell lines differentially expressing LINC00339 were constructed by using small interfering RNA and lentivirus transfection. Cell proliferation was examined by cell counting kit-8 (CCK-8) and colony formation experiments and transwell experiments were used to assess cell invasion and migration abilities. The luciferase assay and RNA immunoprecipitation (RIP) were employed to study the target gene for LINC00339, and western blot analysis was utilized to measure protein expression of the downstream gene. RESULTS: The level of LINC00339 expression in PANC tissues or cells was significantly higher than that in their respective control groups. Interfering expression of LINC00339 could notably inhibit the proliferation, invasion and migration of SW1990 cells, while the over-expressing expression of LINC00339 obviously increased the growth and metastasis abilities of PANC-1 cells. LINC00339 could act as a miR-497-5p sponge, adsorbing miR-497-5p, thereby inhibiting its action by increasing the expression of its target gene IGF1R. The expression of miR-497-5p and its target gene IGF1R could be significantly altered by altering the expression of LINC00339. CONCLUSIONS: LINC00339 was markedly over-expressed in PANC tissues and cells and promoted cell proliferation, invasion, and migration via sponging miR-497-5p, thereby increasing IGF1R expression. Our study could provide a novel target for PANC diagnosis and biotherapy.

Dexmedetomidine preconditioning attenuates ischemia/reperfusion injury in isolated rat hearts with endothelial dysfunction.

BACKGROUND AND PURPOSES: Dexmedetomidine preconditioning (DP) can mimic pharmacological preconditioning and induce cardiac protection. There are controversies on the roles of coronary endothelia in cardioprotection of dexmedetomidine. Herein, we tested the hypothesis that protection of dexmedetomidine is not endothelial dependent in heart against myocardial ischemia/reperfusion (I/R) injury. METHODS: Langendorff-perfused rat hearts were pretreated by 60 mM of potassium to produce endothelial dysfunction (ED), then medicated with dexmedetomidine, and subsequently subjected to 30 min of global ischemia followed by 60 min of reperfusion. To investigate the cardioprotective effect of dexmedetomidine in heart with ED, isolated rat hearts were randomly divided into the following six groups: sham, I/R, DP, ED, ED + I/R, and ED + DP + I/R. Heart rates, left ventricular function, and coronary perfusion pressure were assessed for each heart. Infarct size was evaluated by triphenyltetrazolium chloride staining. High-sensitivity cardiac troponin T (hs-cTNT) of coronary flow perfusion was determined. RESULTS: After the isolated hearts with pretreatment of 60 mM of potassium chloride, diastolic function of coronary endothelia in performance of response to histamine was significantly decreased (P < 0.05). DP attenuated I/R-induced infarct size of the left ventricle (P < 0.05) and decreased hs-cTNT (P < 0.05). Additionally, left ventricular developed pressure, +dp/dtmax, and -dp/dtmax were elevated in rat hearts pretreated with dexmedetomidine. Furthermore, dexmedetomidine-mediated cardiac protection against I/R injury was still remained in isolated hearts with coronary ED. CONCLUSION: Continuous perfusion of 60 mM of potassium for 10 min can produce coronary ED in isolated rat hearts. Dexmedetomidine maintains its protective function against I/R injury in heart with coronary ED. Myocardial protection of dexmedetomidine is non-endothelial function dependent in alleviating I/R injury.

Uncovering novel landscape of cardiovascular diseases and therapeutic targets for cardioprotection via long noncoding RNA-miRNA-mRNA axes.

Protein coding sequences account for around 3% of the human genome, the rest are noncoding RNA (ncRNA) including long ncRNA (lncRNA) and miRNA. Accumulating evidence indicates that lncRNAs and miRNAs are candidate biomarkers for diagnosis, prognosis and therapy of cardiovascular diseases. The lncRNAs act as sponge-like effects on numerous miRNAs, subsequently regulating miRNAs and their targets, mRNA functions. The role of lncRNA-miRNA-mRNA axis in pathogenesis of cardiovascular diseases has been recently reported and highlighted. Herein, this review discusses emerging roles of lncRNA-miRNA-mRNA axis in cardiovascular pathophysiology and regulation, with a novel focus on cardioprotective network activities of the two subgroup ncRNAs.