Long non­coding RNA CTBP1­AS2 upregulates USP22 to promote pancreatic carcinoma progression by sponging miR­141­3p.

Long non­coding RNAs (lncRNAs) feature prominently in pancreatic carcinoma progression. The present study aimed to clarify the biological functions, clinical significance and underlying mechanism of lncRNA CTBP1 antisense RNA 2 (CTBP1­AS2) in pancreatic carcinoma. Reverse transcription­quantitative PCR was performed to assess the expression levels of CTBP1­AS2, microRNA (miR)­141­3p and ubiquitin­specific protease 22 (USP22) mRNA in pancreatic carcinoma tissues and cell lines. Western blotting was used to examine USP22 protein expression in pancreatic carcinoma cell lines. Loss­of­function experiments were used to analyze the regulatory effects of CTBP1­AS2 on proliferation, apoptosis, migration and invasion of pancreatic carcinoma cells. Dual­luciferase reporter assay was used to examine the binding relationship between CTBP1­AS2 and miR­141­3p, as well as between miR­141­3p and USP22. It was demonstrated that CTBP1­AS2 expression was markedly increased in pancreatic carcinoma tissues and cell lines. High CTBP1­AS2 expression was associated with advanced clinical stage and lymph node metastasis of patients. Functional experiments confirmed that knocking down CTBP1­AS2 significantly inhibited pancreatic carcinoma cell proliferation, migration and invasion, and promoted cell apoptosis. In terms of mechanism, it was found that CTBP1­AS2 adsorbed miR­141­3p as a molecular sponge to upregulate the expression level of USP22. In conclusion, lncRNA CTBP1­AS2 may be involved in pancreatic carcinoma progression by regulating miR­141­3p and USP22 expressions; in addition, CTBP1­AS2 may be a diagnostic biomarker and treatment target for pancreatic carcinoma.

The tissue expression levels of SUMO1P 3 may be a reliable prognostic biomarker to predict the clinical outcomes in patients with HCC.

Small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) is a novel identified long non-coding RNA that is upregulated in several cancers and exerts its oncogenic effects via multiple pathways. SUMO1P3 was significantly higher in HCC tissues and cells than in non-cancerous specimens and normal cells. SUMO1P3 knockdown inhibited the proliferation, migration, and invasion of HCC cells. In the present study, we investigated the clinical significance and prognostic value of SUMO1P3 in HCC.A total of 123 patients were pathologically diagnosed as primary HCC and underwent surgical resection at the Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University from March 2014 to November 2019. The expression differences between HCC tissues and matched normal tissues were analyzed using paired Student's t test. Chi-squared test was used for correlation analysis. Survival curves were plotted using the Kaplan-Meier method and were compared via the log-rank test. The independent prognostic value of SUMO1P3 expression was evaluated using results from univariate and multivariate Cox regression models.As revealed by quantitative RT-PCR analysis, SUMO1P 3 expression level was significantly higher in HCC cancer tissues compared with normal adjacent tissues (mean ±â€ŠSD: 4.341 ±â€Š1.320 vs 1.000 ±â€Š0.3666, P < .001). The χ test showed that the SUMO1P 3 expression level was significantly associated with tumor size (P = .031), capsular invasion (P = .011), vascular invasion (P = .004), Edmondson-Steiner grade (P = .002), and TNM stage (P = .001). The patients with high SUMO1P 3 expression showed shorter 5-year overall survival than those with low SUMO1P 3 expression (P = .034; log-rank test). Multivariate regression analysis showed that the status of SUMO1P 3 expression was an independent prognostic factor for overall survival (HR = 2.107, 95% CI: 1.478-9.014, P = .031).The expression levels of SUMO1P 3 may be a reliable prognostic biomarker to predict the clinical outcomes in patients with HCC.

S-allyl-L-cysteine protects hepatocytes from indomethacin-induced apoptosis by attenuating endoplasmic reticulum stress.

Drug-induced liver injury (DILI) can lead to acute liver failure, a lethal condition which may require liver transplantation. Hepatotoxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) accounts for ~ 10% of all DILI. In the current study, we determined whether indomethacin, one of the most commonly used NSAIDS, induced apoptosis in hepatocytes and investigated the underlying mechanism. Meanwhile, we investigated the protective effect of S-allyl-L-cysteine (SAC), an active garlic derivative, on indomethacin-induced hepatocyte apoptosis, and its implication on endoplasmic reticulum (ER) stress. We found that indomethacin triggered ER stress, as indicated by the elevated expression of phosphorylated eukaryotic translation initiation factor 2α (eIF2α), C/EBP homologous protein (CHOP) and spliced XBP1 in a rat liver BRL-3A cell line. Following indomethacin treatment, caspase 3 activation and hepatocyte apoptosis were also observed. Inhibition of ER stress by chemical chaperone 4-phenyl butyric acid alleviated cell apoptosis caused by indomethacin, indicating that ER stress is involved in indomethacin-induced hepatocyte apoptosis. Moreover, SAC abated indomethacin-induced eIF2α phosphorylation, inhibited CHOP upregulation and its nuclear translocation, abrogated the activation of caspase 3 and finally, protected hepatocytes from apoptosis. In conclusion, SAC protects indomethacin-induced hepatocyte apoptosis through mitigating ER stress and may be suitable for development into a potential new therapeutic agent for the treatment of DILI.

S-allyl-l-cysteine (SAC) protects hepatocytes from alcohol-induced apoptosis.

Hepatocyte apoptosis is frequently observed in alcohol-related liver disease (ARLD), which ranks among the 30 leading causes of death worldwide. In the current study, we explored the impact of S-allyl-l-cysteine (SAC), an organosulfur component of garlic, on hepatocyte apoptosis induced by alcohol. Rat liver (BRL-3A) cells were challenged by ethanol with or without SAC treatment. Cell death/viability, reactive oxygen species (ROS) generation, mitochondrial Cytochrome C release, and caspase 3 activity were then examined. We found that ethanol remarkably induced apoptosis of hepatocytes, while SAC treatment rescued ethanol-induced hepatocyte injury, as demonstrated by cell counting kit-8 (CCK8) assay, TUNEL assay, and annexin V/PI staining assay. Ethanol evoked ROS generation in BRL-3A cells, and this was abated by SAC pretreatment, as indicated by 2',7'-dichlorofluorescin diacetate (DCFDA) staining assay. Moreover, ethanol suppressed cellular anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) expression, increased pro-apoptotic protein Bcl-2-associated X protein (Bax) expression, induced mitochondrial Cytochrome C release, and activated the caspase 3-dependent apoptosis pathway in BRL-3A cells. SAC was sufficient to abolish all these changes induced by ethanol, thereby revealing the molecular mechanisms underlying its protective effects. In conclusion, SAC protects hepatocytes from ethanol-induced apoptosis and may be suitable for use as a novel anti-apoptotic agent for treating ARLD.