Gut microbes in gastrointestinal cancers.

Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.

Extracellular Vesicles and Fatty Liver.

Fatty liver is a complex pathological process caused by multiple etiologies. In recent years, the incidence of fatty liver has been increasing year by year, and it has developed into a common chronic disease that seriously affects people's health around the world. It is an important risk factor for liver cirrhosis, liver cancer, and a variety of extrahepatic chronic diseases. Therefore, the early diagnosis and early therapy of fatty liver are important. Except for invasive liver biopsy, there is still a lack of reliable diagnosis and staging methods. Extracellular vesicles are small double-layer lipid membrane vesicles derived from most types of cells. They play an important role in intercellular communication and participate in the occurrence and development of many diseases. Since extracellular vesicles can carry a variety of biologically active substances after they are released by cells, they have received widespread attention. The occurrence and development of fatty liver are also closely related to extracellular vesicles. In addition, extracellular vesicles are expected to provide a new direction for the diagnosis of fatty liver. This article reviews the relationship between extracellular vesicles and fatty liver, laying a theoretical foundation for the development of new strategies for the diagnosis and therapy of fatty liver.

HOXA13 promotes liver regeneration through regulation of BMP-7.

In-depth knowledge of liver regeneration could facilitate the development of therapies for liver injury and liver failure. As a member of the homeobox superfamily, HOXA13 plays an important role in regulating tumorigenesis and development. However, the exact role of HOXA13 in liver regeneration remains unclear. In this study, we confirmed that HOXA13 promotes hepatocyte proliferation both in vivo and in vitro. HOXA13 was upregulated during liver regeneration, and its overexpression further accelerated hepatocyte proliferation and liver function recovery during liver regeneration. Furthermore, we found that HOXA13 promoted hepatocyte proliferation and liver regeneration by upregulating bone morphogenetic protein-7 (BMP-7) mRNA. These findings provide a new potential target for the treatment of liver failure.

Past Exposure to Cigarette Smoke Aggravates Cognitive Impairment in a Rat Model of Vascular Dementia via Neuroinflammation.

Smoking is a risk factor for dementia. Cognitive function can be partially restored after quitting smoking, but still lower than never smoked group. The underlying mechanisms still remain unclear. The effects of smoking cessation combined with cerebral chronic hypoperfusion (CCH) on cognitive function have never been described. Here, we established a cigarette smoking cessation model, a CCH model, and a cigarette smoking cessation plus CCH model. We investigated cognitive function in these models and the mechanisms of the neuroinflammation, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)/cysteine aspartate-specific proteinase (caspase-1)/interleukin- 1ß (IL-1ß) pathway, and eucaryotic initiation factor 2α (eIF2α) /autophagy pathway. We used morris water maze (MWM) and novel object recognition (NOR) test to evaluate cognitive function in rats. Nissl staining was performed to observe cell morphology in the hippocampal CA1 area. A neuroinflammatory marker (glial fibrillary acidic protein, GFAP) was assessed by Western blot analysis and immunohistochemistry staining. IL-1ß levels were detected by ELISA. The protein levels of NLRP3/caspase-1/ IL-1ß and eIF2α/autophagy pathway were evaluated by Western blot analysis. LC3 was assessed by immunofluorescence staining. CCH can affect cognitive function by influencing neuroinflammation, NLRP3/caspase-1/IL-1ß pathway, and eIF2α/autophagy pathway. Past exposure to cigarette smoke can also affect cognitive function by influencing neuroinflammation and NLRP3/caspase-1/IL-1ß pathway, which may be induced by smoking and may not be alleviated after smoking cessation. Past exposure to cigarette smoke does not influence autophagy, which may be increased by smoking and then decrease to normal levels after smoking cessation. Past exposure to smoking can further aggravate cognitive impairment and neuroinflammation in VaD animals: cognitive impairment induced by CCH via neuroinflammation, NLRP3/caspase-1/IL-1ß, and eIF2α/autophagy pathway and cognitive impairment induced by past exposure to cigarette smoke via neuroinflammation and NLRP3/caspase-1/IL-1ß pathway. The combined group had the worst cognitive impairment because of harmful reasons.

Tumor fibrosis correlates with the survival of patients with pancreatic adenocarcinoma and is predictable using clinicoradiological features.

OBJECTIVES: To evaluate the prognostic value of fibrosis for patients with pancreatic adenocarcinoma (PDAC) and preoperatively predict fibrosis using clinicoradiological features. Tumor fibrosis plays an important role in the chemoresistance of PDAC. However, the prognostic value of tumor fibrosis remains contradiction and accurate prediction of tumor fibrosis is required. METHODS: The study included 131 patients with PDAC who underwent first-line surgery. The prognostic value of fibrosis and rounded cutoff fibrosis points for median overall survival (OS) and disease-free survival (DFS) were determined using Cox regression and receiver operating characteristic (ROC) analyses. Then the whole cohort was randomly divided into training (n = 88) and validation (n = 43) sets. Binary logistic regression analysis was performed to select independent risk factors for fibrosis in the training set, and a nomogram was constructed. Nomogram performance was assessed using a calibration curve and decision curve analysis (DCA). RESULTS: Hazard ratios of fibrosis for OS and DFS were 1.121 (95% confidence interval [CI]: 1.082-1.161) and 1.110 (95% CI: 1.067-1.155). ROC analysis identified 40% as the rounded cutoff fibrosis point for median OS and DFS. Tumor diameter, carbohydrate antigen 19-9 level, and peripancreatic tumor infiltration were independent risk factors; areas under the nomogram curve were 0.810 and 0.804 in the training and validation sets, respectively. The calibration curve indicated good agreement of the nomogram, and DCA demonstrated good clinical usefulness. CONCLUSIONS: Tumor fibrosis was associated with poor OS and DFS in patients with PDAC. The nomogram incorporating clinicoradiological features was useful for preoperatively predicting tumor fibrosis. KEY POINTS: • Tumor fibrosis is correlated with poor prognosis in patients with pancreatic adenocarcinoma. • Tumor fibrosis can be categorized according to its association with overall survival and disease-free survival. • A nomogram incorporating carbohydrate antigen 19-9 level, tumor diameter, and peripancreatic tumor infiltration is useful for preoperatively predicting tumor fibrosis.

Role of Non-coding RNA in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality in diabetic population worldwide, characteristic by cardiomyocyte hypertrophy, apoptosis and myocardial interstitial fibrosis and eventually developing into heart failure. Non-coding RNAs, such as microRNAs (miRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs) and other RNAs without the protein encoding function were emerging as a popular regulator in various types of processes during human diseases. The evidences have shown that miRNAs are regulators in diabetic cardiomyopathy, such as insulin resistance, cardiomyocytes apoptosis, and inflammatory, especially their protective effect on heart function. Besides that, the functions of lncRNAs and circRNAs have been gradually confirmed in recent years, and their functions in DCM have become increasingly prominent. We highlighted the nonnegligible roles of non-coding RNAs in the pathological process of DCM and showed the future possibilities of these non-coding RNAs in DCM treatment. In this chapter, we summarized the present advance of the researches in this filed and raised the concern and the prospect in the future.

Circular RNAs as Biomarkers for Cancer.

As a type of novel noncoding RNAs, circular RNAs (circRNAs) have attracted great interest due to its different characteristics from linear RNAs. They are abundantly and stably present in the transcriptome of eukaryotic cells, with development stage specificity and high conservatism. Because circRNAs are not easily degraded by exonuclease RNase R, they can exist more stably in body fluids than linear RNAs. Based on these unique conditions, circRNAs have great potential value as clinical diagnostic and prognostic markers. As the research deepens, more and more evidences suggest that circRNAs may be closely associated with many diseases, especially cancer. Numerous studies have demonstrated the abnormal expression of circRNAs in cancer, and they can regulate the occurrence and progression of cancer by targeting key genes. Abundant circRNAs in tissues and cells can be released into saliva and blood. It is undeniable that circRNAs are a class of promising future biomarkers for cancer diagnosis and prognosis. Here we summarize the researches on circRNAs and cancer over the past few years. We expect this summary to be a stepping stone to further exploration of possible circRNAs as cancer biomarkers.

Circular RNA in Liver: Health and Diseases.

Circular RNA (circRNA) is an important class of noncoding RNA characterized by covalently closed continuous loop structures. In recent years, the various functions of circRNAs have been continuously documented, including effects on cell proliferation and apoptosis and nutrient metabolism. The liver is the largest solid organ in mammals, and it also performs many functions in the body, which is considered to be the busiest organ in the body. At the same time, the liver is vulnerable to multiple pathogenic factors, causing various acute and chronic liver diseases. The pathogenesis of liver disease is still not fully understood. As a rising star for the past few years, circRNAs have been proven involved in the regulation of liver homeostasis and disease. This chapter will explain the role of circRNAs in liver health and diseases and sort out the confusion in the present study.

Sarcopenia in Liver Disease: Current Evidence and Issues to Be sResolved.

Sarcopenia is a common clinical symptom in aging and patients with wasting diseases, characterized by a decreased skeletal muscle mass. As a consequence of lifestyle change, the nonalcoholic fatty liver disease (NAFLD) presents a rising trend. In the past three decades, increasing evidence has proved that sarcopenia is related to NAFLD. In this chapter, we will summarize the emerging evidence of the predictive role of sarcopenia in NAFLD and review the diagnosis value, feasible mechanism, and therapy strategies of sarcopenia in NAFLD. Sarcopenia is a potential risk factor for NAFLD, and targeting sarcopenia can benefit NAFLD to some extent.

miR-224 Controls Human Colorectal Cancer Cell Line HCT116 Proliferation by Targeting Smad4.

Background: Better understanding the molecular mechanisms responsible for the genesis and progression of colorectal cancer would help advance the novel therapeutics. miR-224 has been identified to be elevated in colorectal cancer and promote human colorectal cancer cell line SW480 proliferation and invasion. However, the effect of miRNAs on cancer cell proliferation could be significantly changeable among different cell lines. HCT116 is a commonly used cell line for colorectal cancer study and the target gene responsible for the function of miR-224 in its proliferation is unclear. Methods: miR-224 expression was determined by quantitative reverse transcription polymerase chain reactions (PCRs) in human colorectal cancer tissues compared with their corresponding matched peritumoral tissues. HCT116 cell viability and cell proliferation were determined by CCK-8, EdU incorporation assays and flow cytometry for cell cycle. Target gene of miR-224 was confirmed by Western blots and siRNA for Smad4. Results: miR-224 was significantly increased by 29.49 fold in colorectal cancer tissues compared with their corresponding matched peritumoral tissues based on 12 colorectal cancer patients. miR-224 mimic significantly increased HCT116 cell viability, EdU positive cells rate, and decreased G1 phase cell population and increased S phase cell population. miR-224 inhibitor had opposite effects. Smad4 could be negatively regulated by miR-224 in HCT116 cells and was responsible for its effects in proliferation. Conclusion: miR-224 mediates HCT116 cell proliferation by targeting Smad4.

C/EBPB-CITED4 in Exercised Heart.

C/EBPB is a crucial transcription factor, participating in a variety of biological processes including cell proliferation, differentiation and development. In the cardiovascular system, C/EBPB-CITED4 signaling is known as a signaling pathway mediating exercise-induced cardiac growth. After its exact role in exercised heart firstly reported in 2010, more and more evidence confirmed that. MicroRNA (e.g. miR-222) and many molecules (e.g. Alpha-lipoic acid) can regulate this pathway and then involve in the cardiac protection effect induced by endurance exercise training. In addition, in cardiac growth during pregnancy, C/EBPB is also a required regulator. This chapter will give an introduction of the C/EBPB-CITED4 signaling and the regulatory network based on this signaling pathway in exercised heart.

miR-149 controls non-alcoholic fatty liver by targeting FGF-21.

Non-alcoholic fatty liver disease (NAFLD), a lipid metabolism disorder characterized by the accumulation of intrahepatic fat, has emerged as a global public health problem. However, its underlying molecular mechanism remains unclear. We previously have found that miR-149 was elevated in NAFLD induced by high-fat diet mice model, whereas decreased by a 16-week running programme. Here, we reported that miR-149 was increased in HepG2 cells treated with long-chain fatty acid (FFA). In addition, miR-149 was able to promote lipogenesis in HepG2 cells in the absence of FFA treatment. Moreover, inhibition of miR-149 was capable of inhibiting lipogenesis in HepG2 cells in the presence of FFA treatment. Meanwhile, fibroblast growth factor-21 (FGF-21) was identified as a target gene of miR-149, which was demonstrated by the fact that miR-149 could negatively regulate the protein expression level of FGF-21, and FGF-21 was also responsible for the effect of miR-149 inhibitor in decreasing lipogenesis in HepG2 cells in the presence of FFA treatment. These data implicate that miR-149 might be a novel therapeutic target for NAFLD.

MiR-221 Promotes Capan-2 Pancreatic Ductal Adenocarcinoma Cells Proliferation by Targeting PTEN-Akt.

BACKGROUND/AIMS: MicroRNAs (miRNAs, miRs) have emerged as critical regulators of cancer cell proliferation. The effect of miR-221 on cancer cell growth could be significantly changeable in different cell lines. Although miR-221 was reported to promote the cell growth of pancreatic ductal adenocarcinoma (PDAC) cells, its role in Capan-2 cell line is largely unknown. METHODS: Capan-2 cells were transfected with miR-221 mimics, inhibitors, or negative controls. Cell Counting Kit-8 was used to determine cell viability. EdU staining and cell cycle analysis were used to measure cell proliferation. Western blotting was used to detect the expression levels of PTEN and phospho-Akt. The PI3K-Akt pathway activator SC-79 and inhibitor LY294002 were used to perform the rescue experiment in determining cell proliferation. RESULTS: Overexpressing miR-221 significantly increased cell vitality and promoted cell proliferation and G1-to-S phase transition of the cell cycle in Capan-2 cells, while inhibition of miR-221 decreased that. The protein level of PTEN in Capan-2 cells was downregulated by overexpressing miR-221, while upregulated by inhibiting miR-221. Consistently, enhanced phosphorylation of AktSer473 was observed in miR-221 overexpressed Capan-2 cells, and the opposite result was found in miR-221 inhibited cells. LY294002 restored the pro-proliferation effect of miR-221 on Capan-2 cells, while SC-79 had no additional effect on cell proliferation in Capan-2 cells transfected with miR-221 mimics. CONCLUSION: Our study indicates that miR-221 is an oncogenic miRNA which promotes Capan-2 cells proliferation by targeting PTEN-Akt pathway.

Therapeutic inhibition of phospholipase D1 suppresses hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents a leading cause of deaths worldwide. Novel therapeutic targets for HCC are needed. Phospholipase D (PD) is involved in cell proliferation and migration, but its role in HCC remains unclear. In the present study, we show that PLD1, but not PLD2, was overexpressed in HCC cell lines (HepG2, Bel-7402 and Bel-7404) compared with the normal human L-02 hepatocytes. PLD1 was required for the proliferation, migration and invasion of HCC cells without affecting apoptosis and necrosis, and PLD1 overexpression was sufficient to promote those effects. By using HCC xenograft models, we demonstrated that therapeutic inhibition of PLD1 attenuated tumour growth and epithelial-mesenchymal transition (EMT) in HCC mice. Moreover, PLD1 was found to be highly expressed in tumour tissues of HCC patients. Finally, mTOR (mechanistic target of rapamycin) and Akt (protein kinase B) were identified as critical pathways responsible for the role of PLD1 in HCC cells. Taken together, the present study indicates that PLD1 activation contributes to HCC development via regulation of the proliferation, migration and invasion of HCC cells, as well as promoting the EMT process. These observations suggest that inhibition of PLD1 represents an attractive and novel therapeutic modality for HCC.

MicroRNA-21 Contributes to Liver Regeneration by Targeting PTEN.

BACKGROUND: Multiple microRNAs (miRNAs, miRs), including miR-21, have been documented to be critical regulators of liver regeneration, but the mechanism underlying their roles in hepatocyte proliferation and cell cycle progression is still far from understood. MATERIAL/METHODS: miR-21 levels were determined using qRT-PCRs in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h). Cell proliferation was determined by use of a cell-counting kit-8 (CCK-8), EdU incorporation staining, and flow cytometry. Phosphatase and tensin homolog (PTEN) expressions were determined using qRT-PCR and Western blot analysis. PTEN siRNA was used to perform the rescue experiment. RESULTS: A marked upregulation of miR-21 was observed in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h) compared to 0 h after PH (PH-0 h). Overexpression of miR-21 was associated with increased proliferation and a rapid G1-to-S phase transition of the cell cycle in BNL CL.2 normal liver cells in vitro. In addition, we showed that PTEN expression was inversely correlated with miR-21 in BNL CL.2 cells and demonstrated that PTEN expression is lower in mouse livers at PH-48 h. Moreover, the presence of PTEN siRNA significantly abolished the suppressive effect of miR-21 inhibitor on hepatocyte proliferation. CONCLUSIONS: miR-21 overexpression contributes to liver regeneration and hepatocyte proliferation by targeting PTEN. Upregulation of miR-21 might be a useful therapeutic strategy to promote liver regeneration.

Key genes associated with prognosis and metastasis of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC metastasis remains unknown. METHODS: Differentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (n = 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1). RESULTS: A total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (PCOLCE), prolyl 4-hydroxylase subunit beta (P4HB), collagen type VI alpha 2 (COL6A2) and collagen type VI alpha 3 (COL6A3). Patients with higher expression of these key genes had worse survival than those with lower expression. In vitro experiments revealed that the mRNA expression levels of PCOLCE, P4HB and COL6A2 were three times higher and that of COL6A3 mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance. CONCLUSION: PCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.

Exercise-Induced ADAR2 Protects against Nonalcoholic Fatty Liver Disease through miR-34a.

Nonalcoholic fatty liver disease (NAFLD) is a growing health problem that is closely associated with insulin resistance and hereditary susceptibility. Exercise is a beneficial approach to NAFLD. However, the relief mechanism of exercise training is still unknown. In this study, mice on a normal diet or a high-fat diet (HFD), combined with Nω-nitro-L-arginine methyl ester, hydrochloride (L-NAME) mice, were either kept sedentary or were subjected to a 12-week exercise running scheme. We found that exercise reduced liver steatosis in mice with diet-induced NAFLD. The hepatic adenosine deaminases acting on RNA 2 (ADAR2) were downregulated in NAFLD and were upregulated in the liver after 12-week exercise. Next, overexpression of ADAR2 inhibited and suppression promoted lipogenesis in HepG2 cells treated with oleic acid (OA), respectively. We found that ADAR2 could down-regulate mature miR-34a in hepatocytes. Functional reverse experiments further proved that miR-34a mimicry eliminated the suppression of ADAR2 overexpression in lipogenesis in vitro. Moreover, miR-34a inhibition and mimicry could also affect lipogenesis in hepatocytes. In conclusion, exercise-induced ADAR2 protects against lipogenesis during NAFLD by editing miR-34a. RNA editing mediated by ADAR2 may be a promising therapeutic candidate for NAFLD.

Risk Factors of Atrial Arrhythmia in Patients With Liver Cirrhosis: A Retrospective Study.

Background and Objectives: Liver cirrhosis is known to be associated with atrial arrhythmia. However, the risk factors for atrial arrhythmia in patients with liver cirrhosis remain unclear. This retrospective study aimed to investigate the risk factors for atrial arrhythmia in patients with liver cirrhosis. Methods: In the present study, we collected data from 135 patients with liver cirrhosis who were admitted to the Department of Gastroenterology at Shanghai Tongji Hospital. We examined the clinical information recorded, with the aim of identifying the risk factors for atrial arrhythmia in patients with liver cirrhosis. Multiple logistic regression analysis was used to screen for significant factors differentiating liver cirrhosis patients with atrial arrhythmia from those without atrial arrhythmia. Results: The data showed that there were seven significantly different factors that distinguished the group with atrial arrhythmia from the group without atrial arrhythmia. The seven factors were age, white blood cell count (WBC), albumin (ALB), serum Na+, B-type natriuretic peptide (BNP), ascites, and Child-Pugh score. The results of multivariate logistic regression analysis suggested that age (ß = 0.094, OR = 1.098, 95% CI 1.039-1.161, P = 0.001) and ascites (ß =1.354, OR = 3.874, 95% CI 1.202-12.483, P = 0.023) were significantly associated with atrial arrhythmia. Conclusion: In the present study, age and ascites were confirmed to be risk factors associated with atrial arrhythmia in patients with liver cirrhosis.

The in vitro effects of phospholipase D1-mTOR axis in liver fibrogenesis.

AIMS: The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis progression. Phospholipase D (PLD) enzymes participate in multiple cellular activities. However, whether and how PLD regulates HSCs activation remain elusive. MAIN METHODS: The expression of intrahepatic PLD1 and PLD2 was determined in CCl4-induced mouse liver fibrosis models by western blot and immunohistochemistry. Cell model of liver fibrogenesis was constructed using rat HSCs line (HSC-T6) treated with recombinant transforming growth factor ß1 (TGFß1). Fibrogenesis was evaluated on the aspects of proliferation, expression of pro-fibrogenic markers and migration. The effects mediated by PLD1-mTOR axis on TGFß1-induced fibrogenesis were evaluated using HSC-T6 treated with small-molecular PLD1 inhibitors, PLD1-SiRNA, rapamycin (mTOR inhibitor) and MHY1485 (mTOR activator). KEY FINDINGS: Significant increase of PLD1, not PLD2 was documented in CCl4-induced cirrhotic compared to normal liver tissues. Suppression of PLD1 activities by PLD inhibitors or down-regulation of PLD1 expression in HSC-T6 could significantly restrain TGFß1-induced fibrogenesis, as reflected by decreased cell proliferation and reduced expression of pro-fibrogenic markers. Besides, either PLD1 inhibitor or PLD1-SiRNA significantly inhibited mTOR activity of HSC-T6. Moreover, PLD1 inhibitors not only exhibited similar effects with rapamycin in TGFß1-induced fibrogenesis, but also blunted MHY1485 enhanced cell proliferation of HSC-T6. SIGNIFICANCE: The PLD1-mTOR axis of HSCs could be therapeutically targeted in advanced liver fibrosis.

miR-19b-3p promotes human pancreatic cancer Capan-2 cells proliferation by targeting phosphatase and tension homolog.

BACKGROUND: Pancreatic cancer is a common cancer with a poor prognosis and an increasing morbidity. miR-19b-3p has been implicated in some cancers, however, its role in pancreatic cancer is unclear. METHODS: Human pancreatic cancer cell line Capan-2 cells were transfected with miR-19b-3p mimic and inhibitor. Cell proliferation was measured by 5-Ethynyl-2'-deoxyuridine (EdU) staining assays. Cell cycle of Capan-2 cells was examined by flow cytometry. The expression of phosphatase and tension homolog (PTEN) was determined by real-time quantitative polymerase chain reaction (PCR) and western blotting analysis. Functional rescue experiments were performed through PTEN overexpression and miR-19b-3p mimic by using EdU staining assays. RESULTS: miR-19b-3p mimic significantly increased miR-19b-3p while miR-19b-3p inhibitor decreased that. EdU staining showed that miR-19b-3p overexpression promoted Capan-2 cells proliferation while miR-19b-3p inhibition decreased that. Flow cytometry analysis of cell cycle indicated that miR-19b-3p overexpression increased the percentage of Capan-2 cells in S phase while miR-19b-3p inhibition decreased that. PTEN was confirmed to be a target gene of miR-19b-3p and PTEN overexpression eliminated the pro-proliferation effects of miR-19b-3p in Capan-2 cells. CONCLUSIONS: Our study demonstrates that miR-19b-3p promotes Capan-2 cells proliferation by targeting PTEN.