TAGLN2 targeted control of ARPC5-mediated activation of the MEK/ERK signaling pathway influences the proliferation, invasion, and metastasis of pancreatic cancer cells.

PURPOSE: Pcancreatic cancer (PC) is a common tumor of the digestive tract with an insidious onset and high malignancy potential. Currently, surgery is the only effective treatment modality. Therefore, it is crucial to discover new targeted therapeutic modalities. We studied whether transgelin 2 (TAGLN2) targeted control of actin-related protein 2/3 complex subunit 5 (ARPC5)-mediated activation of the MEK/ERK signaling pathway to Influences the proliferation, invasion, and metastasis of pancreatic cancer cells. METHODS: The effects of TAGLN2 overexpression and knockdown on the proliferative viability and invasive metastatic ability of pancreatic cancer cells were verified through in vitro and in vivo assays via constructing a stable lentiviral transfection of human pancreatic cancer cell lines PANC-1 and SW1990. Bioinformatics analysis was used to predict the relationship between TAGLN2 and ARPC5. These findings were subsequently verified through protein profiling, immunofluorescence (IF), and coimmunoprecipitation (CO-IP) assays. In vitro experiments were also conducted to confirm the effect of TAGLN2 modulation on ARPC5 expression, which subsequently affects the proliferation and invasive metastatic ability of pancreatic cancer cells. The study analyzed the relationship between TAGLN2 and the MEK/ERK signaling pathway through bioinformatics and in vitro experiments with the MEK signaling pathway inhibitor U0126. RESULTS: TAGLN2 is expressed at high levels in pancreatic cancer cell lines, and its expression is positively correlated with poor prognosis of pancreatic cancer. ARPC5 is a direct target of TAGLN2 and is associated with the MEK/ERK signaling pathway. In vivo and ex vivo experiments confirmed that overexpression of TAGLN2 promoted the proliferation, invasion, and metastasis of pancreatic cancer cells, and silencing ARPC5 reversed these effect. CONCLUSION: Our research revealed that TAGLN2 protein binds to ARPC5 protein and contributes to increased ARPC5 expression and activation of the MEK/ERK signaling pathway. This activation promotes pancreatic cancer cell growth, infiltration, and spread. Hence, TAGLN2 is a potential viable therapeutic target in pancreatic cancer and represents a novel therapeutic approach.

Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target.

PURPOSE: Pancreatic cancer (PC) is a highly malignant tumor that poses a severe threat to human health. Brain glycogen phosphorylase (PYGB) breaks down glycogen and provides an energy source for tumor cells. Although PYGB has been reported in several tumors, its role in PC remains unclear. METHODS: We constructed a risk diagnostic model of PC-related genes by WGCNA and LASSO regression and found PYGB, an essential gene in PC. Then, we explored the pro-carcinogenic role of PYGB in PC by in vivo and in vitro experiments. RESULTS: We found that PYGB, SCL2A1, and SLC16A3 had a significant effect on the diagnosis and prognosis of PC, but PYGB had the most significant effect on the prognosis. Pan-cancer analysis showed that PYGB was highly expressed in most of the tumors but had the highest correlation with PC. In TCGA and GEO databases, we found that PYGB was highly expressed in PC tissues and correlated with PC's prognostic and pathological features. Through in vivo and in vitro experiments, we found that high expression of PYGB promoted the proliferation, invasion, and metastasis of PC cells. Through enrichment analysis, we found that PYGB is associated with several key cell biological processes and signaling pathways. In experiments, we validated that the MAPK/ERK pathway is involved in the pro-tumorigenic mechanism of PYGB in PC. CONCLUSION: Our results suggest that PYGB promotes PC cell proliferation, invasion, and metastasis, leading to poor patient prognosis. PYGB gene may be a novel diagnostic biomarker and gene therapy target for PC.

PELI1: key players in the oncogenic characteristics of pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly malignant gastrointestinal tumor, which is characterized by difficulties in early diagnosis, early metastasis, limited therapeutic response and a grim prognosis. Therefore, it is imperative to explore potential therapeutic targets for PC. Currently, although the involvement of the Pellino E3 Ubiquitin Protein Ligase 1 (PELI1) in the human growth of some malignant tumors has been demonstrated, its association with PC remains uncertain. METHODS: Bioinformatics, qRT-PCR, Western blot and IHC were used to detect the expression of PELI1 in pancreas or PC tissues and cells at mRNA and protein levels. The effects of PELI1 on the proliferation and metastatic ability of pancreatic cancer in vitro and in vivo were investigated using CCK8, cloning formation, EdU, flow cytometry, IHC, Transwell assay, wound healing, nude mice subcutaneous tumorigenesis and intrasplenic injection to construct a liver metastasis model. The interactions of PELI1 with proteins as well as the main functions and pathways were investigated by protein profiling, Co-IP, GST-pull down, Immunofluorescence techniques, immunohistochemical co-localization and enrichment analysis. The rescue experiment verified the above experimental results. RESULTS: The mRNA and protein expression levels of PELI1 in PC tissues were upregulated and were associated with poor prognosis of patients, in vitro and in vivo experiments confirmed that PELI1 can affect the proliferation and metastatic ability of PC cells. Co-IP, GST-pull down, and other experiments found that PELI1 interacted with Ribosomal Protein S3 (RPS3) through the FHA structural domain and promoted the polyubiquitination of RPS3 in the K48 chain, thereby activates the PI3K/Akt/GSK3ß signaling pathway. Moreover, ubiquitinated degradation of RPS3 further reduces Tumor Protein P53 (p53) protein stability and increases p53 degradation by MDM2 Proto-Oncogene (MDM2). CONCLUSION: PELI1 is overexpressed in PC, which increased ubiquitination of RPS3 proteins and activates the PI3K/Akt/GSK3ß signaling pathway, as well as reduces the protective effect of RPS3 on p53 and promotes the degradation of the p53 protein, which facilitates the progression of PC and leads to a poor prognosis for patients. Therefore, PELI1 is a potential target for the treatment of PC.

A study on the role of Taxifolin in inducing apoptosis of pancreatic cancer cells: screening results using weighted gene co-expression network analysis.

Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor in the pancreas. The incomplete understanding of cancer etiology and pathogenesis, as well as the limitations in early detection and diagnostic methods, have created an urgent need for the discovery of new therapeutic targets and drugs to control this disease. As a result, the current therapeutic options are limited. In this study, the weighted gene co-expression network analysis (WGCNA) method was employed to identify key genes associated with the progression and prognosis of pancreatic adenocarcinoma (PAAD) patients in the Gene Expression Profiling Interactive Analysis (GEPIA) database. To identify small molecule drugs with potential in the treatment of pancreatic adenocarcinoma (PAAD), we compared key genes to the reference dataset in the CMAP database. First, we analyzed the antitumor properties of small molecule drugs using cell counting kit-8 (CCK-8), AO/EB and Transwell assays. Subsequently, we integrated network pharmacology with molecular docking to explore the potential mechanisms of the identified molecules' anti-tumor effects. Our findings indicated that the progression and prognosis of PAAD patients in pancreatic cancer were associated with 11 genes, namely, DKK1, S100A2, CDA, KRT6A, ITGA3, GPR87, IL20RB, ZBED2, PMEPA1, CST6, and MUC16. These genes were filtered based on their therapeutic potential through comparing them with the reference dataset in the CMAP database. Taxifolin, a natural small molecule drug with the potential for treating PAAD, was screened by comparing it with the reference dataset in the CMAP database. Cell-based experiments have validated the potential of Taxifolin to facilitate apoptosis in pancreatic cancer cells while restraining their invasion and metastasis. This outcome is believed to be achieved via the HIF-1 signaling pathway. In conclusion, this study provided a theoretical basis for screening genes related to the progression of pancreatic cancer and discovered potentially active small molecule drugs. The experimental results confirm that Taxifolin has the ability to promote apoptosis in pancreatic cancer cells.

Analysis and validation of the potential of the MYO1E gene in pancreatic adenocarcinoma based on a bioinformatics approach.

Pancreatic adenocarcinoma (PAAD) is a common digestive cancer, and its prognosis is poor. Myosin 1E (MYO1E) is a class I myosin family member whose expression and function have not been reported in PAAD. In the present study, bioinformatics analysis was used to explore the expression levels of MYO1E in PAAD and its prognostic value, and the immunological role of MYO1E in PAAD was analyzed. The study revealed that a variety of malignancies have substantially increased MYO1E expression. Further investigation demonstrated that PAAD tissues exhibited greater levels of MYO1E mRNA and protein expression than normal tissues. High MYO1E expression is associated with poor prognosis in patients with PAAD. MYO1E expression was also associated with pathological stage in patients with PAAD. Functional enrichment analysis demonstrated that MYO1E was linked to multiple tumor-related mechanisms in PAAD. The pancreatic adenocarcinoma tumor microenvironment (TME) was analyzed and it was revealed that MYO1E expression was positively associated with tumor immune cell infiltration. In addition, MYO1E was closely associated with some tumor chemokines/receptors and immune checkpoints. In vitro experiments revealed that the suppression of MYO1E expression could inhibit pancreatic adenocarcinoma cell proliferation, invasion and migration. Through preliminary analysis, the present study evaluated the potential function of MYO1E in PAAD and its function in TME, and MYO1E may become a potential biomarker for PAAD.

FBXO28 promotes proliferation, invasion, and metastasis of pancreatic cancer cells through regulation of SMARCC2 ubiquitination.

The E3 ligase F-box only protein 28 (FBXO28) belongs to the F-box family of proteins that play a critical role in tumor development. However, the potential function of FBXO28 in pancreatic cancer (PC) and its molecular mechanism remain unclear. In this study, we examined FBXO28 expression in PC and its biological role and explored the mechanism of FBXO28-mediated proliferation, invasion, and metastasis of PC cells. Compared with paracancerous tissues and human normal pancreatic ductal epithelial cells, FBXO28 was highly expressed in PC tissues and cell lines. High expression of FBXO28 was negatively correlated with the survival prognosis of patients with PC. Functional assays indicated that FBXO28 promoted PC cell proliferation, invasion, and metastasis in vitro and in vivo. Furthermore, immunoprecipitation-mass spectrometry was used to identify SMARCC2 as the target of FBXO28; upregulation of SMARCC2 can reverse the effect of overexpression of FBXO28 on promoting the proliferation, invasion, and metastasis of PC cells. Mechanistically, FBXO28 inhibited SMARCC2 expression in post-translation by increasing SMARCC2 ubiquitination and protein degradation. In conclusion, FBXO28 has a potential role in PC, possibly promoting PC progression through SMARCC2 ubiquitination. Thus, FBXO28 might be a potential treatment target in PC.

[Retracted] MicroRNA­526a targets p21­activated kinase 7 to inhibit tumorigenesis in hepatocellular carcinoma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the data shown for the Transwell cell migration and invasion assays in Fig. 2C and D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 837­844, 2017; DOI: 10.3892/mmr.2017.6658].

The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway.

The pathogenic mechanisms of pancreatic cancer (PC) are still not fully understood. Ubiquitination modifications have a crucial role in tumorigenesis and progression. Yet, the role of MINDY2, a member of the motif interacting with Ub-containing novel DUB family (MINDY), as a newly identified deubiquitinating enzyme, in PC is still unclear. In this study, we found that MINDY2 expression is elevated in PC tissue (clinical samples) and was associated with poor prognosis. We also found that MINDY2 is associated with pro-carcinogenic factors such as epithelial-mesenchymal transition (EMT), inflammatory response, and angiogenesis; the ROC curve suggested that MINDY2 has a high diagnostic value in PC. Immunological correlation analysis suggested that MINDY2 is deeply involved in immune cell infiltration in PC and is associated with immune checkpoint-related genes. In vivo and in vitro experiments further suggested that elevated MINDY2 promotes PC proliferation, invasive metastasis, and EMT. Meanwhile, actinin alpha 4 (ACTN4) was identified as a MINDY2-interacting protein by mass spectrometry and other experiments, and ACTN4 protein levels were significantly correlated with MINDY2 expression. The ubiquitination assay confirmed that MINDY2 stabilizes the ACTN4 protein level by deubiquitination. The pro-oncogenic effect of MINDY2 was significantly inhibited by silencing ACTN4. Bioinformatics Analysis and Western blot experiments further confirmed that MINDY2 stabilizes ACTN4 through deubiquitination and thus activates the PI3K/AKT/mTOR signaling pathway. In conclusion, we identified the oncogenic role and mechanism of MINDY2 in PC, suggesting that MINDY2 is a viable candidate gene for PC and may be a therapeutic target and critical prognostic indicator.

Identification and validation of a potential key gene SGOL1 for poor prognosis in hepatocellular carcinoma based on a bioinformatics approach.

Objective: Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. Shugoshin 1 (SGOL1) plays a crucial role in cell mitosis and its aberrant expression level in human tumors has shown to promote chromosomal instability (CIN) and accelerate tumor growth. SGOL1 expression level in HCC cells and tissues, whether it has an influence on HCC patients' prognosis, and its mechanism of action have not yet been studied. Methods: We carried out the bioinformatics analysis of SGOL1 expression level and survival analysis in 8 different malignancies, including HCC. In addition, we analyzed SGOL1 expression level in HCC tissues, as well as HCC patients' clinical features, enrichment analysis of SGOL1 function and mechanism of action in HCC and tumor immune cells. The effects of SGOL1 expression level and cell viability on HCC were confirmed by in vitro cytological assays. Results: It was found that SGOL1 mRNA expression level was significantly higher in several tumor tissues, including HCC, than in corresponding normal tissues, and the elevated SGOL1 expression level was strongly associated with HCC patients' poor prognosis. It was also revealed that SGOL1 expression level in HCC tissue was positively correlated with disease stage, tumor grade, and tumor size, and the results of multivariate logistic regression analysis showed that SGOL1 was one of the independent influential factors of the prognosis of HCC. Enrichment analysis revealed that SGOL1 expression level in HCC tissue was mainly associated with tumor proliferation, cell cycle, and other factors. The results of the immune infiltration analysis indicated that SGOL1 expression level was associated with immune cell infiltration and immune checkpoints in HCC. In vitro experiments demonstrated the high SGOL1 expression level in HCC tissues and cells, and silencing of SGOL1 resulted in altered cell cycle markers and decreased proliferation, invasion, and migration of HCC cells. Conclusion: The findings revealed that SGOL1 is highly expressed in HCC tissues, it is a biomarker of a poor prognosis, which may be related to immune cell infiltration in HCC, and may enhance the proliferation, invasion, and migration of HCC cells. The results may provide new insights into targeted treatment of HCC and improve HCC patients' prognosis.

FBXW7 Reduces the Cancer Stem Cell-Like Properties of Hepatocellular Carcinoma by Regulating the Ubiquitination and Degradation of ACTL6A.

Cancer stem cells (CSCs) comprise a subset of tumor cells that can initiate tumorigenesis and promote tumor advance. A previous study showed that the expression of FBXW7 in hepatocellular carcinoma (HCC) clinical samples was lower than that in the adjacent nontumor tissues and was negatively correlated with the invasion and migration of HCC cells. However, the biological characteristics and the underlying molecular mechanisms of FBXW7 in HCC stemness are yet to be elucidated. In present study, we found that FBXW7 participates in the self-renewal, tumorigenicity, sorafenib therapy, and stem cell-like properties of HCC cells in vivo and in vitro. The upregulation of FBXW7 inhibited the stemness and reduced the tumorigenicity and drug resistance of HCC cells. Mechanistically, proteins binding to FBXW7 were identified by coimmunoprecipitation and protein colocalization assays. We confirmed ACTL6A as a novel downstream target for FBXW7. The in vivo ubiquitination assay showed that FBXW7 repressed HCC malignancy by regulating the oncogenic activity of ACTL6A in a ubiquitin-dependent manner. Furthermore, we found that ACTL6A overexpression inversed the self-renewal abilities and tumorigenic abilities depressed by overexpressing FBXW7. The current findings suggested that FBXW7 reduces the stemness of HCC cells by targeting and degrading ACTL6A and provides a novel target for the diagnosis and treatment of HCC.

Early prevention and risk factors analysis of portal vein system thrombosis after laparoscopic splenectomy and pericardial devascularization.

BACKGROUND: Portal vein system thrombosis (PVST) is a common postoperative complication brought by laparoscopic splenectomy and pericardial disconnection (LSD) among patients who suffered from portal hypertension and hypersplenism. This research lies mainly in probing into the risk factors of PVST and evaluating the effects of warfarin on PVST prevention. MATERIALS AND METHODS: We took 131 individuals who have carried out LSD from January 2015 to January 2021. Patients were divided into warfarin group (n = 68) and aspirin group (n = 63). Meanwhile, thrombosis factors were analyzed in PVST arm (n = 48) and non-PVST arm (n = 83). RESULTS: We analyzed the early postoperative anticoagulation effect, 20 patients (29.4%) in the warfarin group developed PVST, and 28 patients (44.4%) in the aspirin group. The chance to PVST during the first year after operation was lower in the warfarin group than in the aspirin group (F = 13.43, P = 0.006). Risk factors for PVST were analyzed, and diabetes, the diameter of the portal vein and splenic vein, and the velocity of portal blood flow were statistically significant between the PVST arm and non-PVST arm (P < < 0.05). Multiple logistic regression analyses have shown that diabetes, portal vein diameter, splenic vein diameter, and the velocity of portal blood flow were the risk factors of PVST. CONCLUSIONS: The portal vein diameter, splenic vein diameter, portal vein flow velocity, and diabetes are risk factors for the PVST after LSD. The prophylactic use of warfarin anticoagulation markedly decreases the probability of occurrence of the PVST in patients with portal hypertension after LSD compared to aspirin.

FAM126A interacted with ENO1 mediates proliferation and metastasis in pancreatic cancer via PI3K/AKT signaling pathway.

Pancreatic cancer (PC) is a common digestive system carcinoma with high mortality rate mostly due to aberrant growth and distant metastasis. Current researches demonstrated that Family Sequence Similarities (FAMs) have been involving in tumor development, and which subfamily has the function of promoting or inhibiting tumors and its in-depth molecular mechanism remains unclear. Based on the Gene Expression Omnibus (GEO), the Gene Expression Profiling Interactive Analysis (GEPIA2), we observed that FAM126A is in high expressed level among PC tissues and contributes to worse progression of PC, which was validated by PC tissue microarray. Function assay indicated that overexpression of FAM126A accelerates PC cell proliferation, invasion and migration in vitro, as well as liver cancer metastasis in vivo. Further, we found that FAM126A induces epithelial-mesenchymal transition (EMT), including the downregulation of E-cadherin epithelial marker expression, and the upregulation of N-cadherin, Vimentin, and Snail, mesenchymal marker expression. By co-localization and co-immunoprecipitation assays, we confirmed that FAM126A directly interacts with ENO1, which was a key activator of the PI3K/AKT signaling pathway. Furthermore, ENO1 knockdown reversed cell proliferation, migration, and invasion of PC cells promoted by FAM126A overexpression in vitro and in vivo. In general, these results verified FAM126A is an oncogene interacting with ENO1 in PC by activating PI3K/AKT signaling pathway.

LncRNA ELF3-AS1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma.

Background: Expression of long noncoding RNA (lncRNA) ELF3 antisense RNA 1 (ELF3-AS1) is observed in some cancers, while its role in hepatocellular carcinoma (HCC) is unclear. The study aimed to investigate the relationship between ELF3-AS1 and HCC based on database, bioinformatics, and statistical analysis. Methods: In this study, Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, gene set enrichment analysis (GSEA), and immunoinfiltration analysis were used to assess the relationship between ELF3-AS1 expression and clinical characteristics of HCC patients, the relationship between ELF3-AS1 expression and prognosis of HCC patients, and the possible functions of ELF3-AS1 in HCC. Results: High expression of ELF3-AS1 in patients with HCC was related to T stage (P < 0.001), gender (P = 0.006), residual tumor (P = 0.008), histologic grade (P < 0.001), adjacent hepatic tissue inflammation (P = 0.011), AFP (P < 0.001), and vascular invasion (P = 0.028). High ELF3-AS1 expression was associated with poor overall survival (OS) (P = 0.001) and DSS (P = 0.047). ELF3-AS1 expression (P = 0.011) was independently correlated with OS in HCC patients. In the high ELF3-AS1 expression group, GPCR-radioligand binding, M phase, Class A/1 (rhodopsin-like receptors), cell cycle checkpoints, translation, mitotic metaphase and anaphase, signaling by robo receptors, keratinization, and rRNA processing were differentially enriched by GESA. ELF3-AS1 expression was associated with immune infiltrating cells. Conclusions: ELF3-AS1 expression was associated with poor prognosis in HCC. ELF3-AS1 expression was significantly associated with immune infiltration. ELF3-AS1 is a promising biomarker that can be used for the diagnosis and prognosis of HCC.

Long Non-coding RNA MAFG-AS1 Promotes Cell Proliferation, Migration, and EMT by miR-3196/STRN4 in Drug-Resistant Cells of Liver Cancer.

Long non-coding RNAs (lncRNAs) have been shown to participate in the development and progression of several different types of cancer. Past studies indicated that lncRNA MAFG-antisense 1 (AS1) promotes colorectal cancer. However, the role of MAFG-AS1 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study is to examine the effect of lncRNA MAFG-AS1 on drug resistance HCC. The results indicated that MAFG-AS1 is upregulated in drug-resistant cells. Further, MAFG-AS1 promotes growth and migration of HCC by upregulating STRN4 through absorbing miR-3196. Thus, LncRNA MAFA-AS1 may become a novel target to treat HCC patients.

Endoscopic management of biliary ascariasis: A case report.

BACKGROUND: Biliary ascariasis is rare but remains the most common parasitic infection in remote areas and in people with poor medical conditions. Here, we reported a case of biliary ascariasis in order to raise awareness of possible parasitic infections. CASE SUMMARY: A 68-year-old female was admitted to the emergency room of the Affiliated Hospital of Guizhou Medical University on 28 September 2017, with chief complaint of pain in the right upper abdomen. Ultrasonography of the abdomen showed that the upper segment of the common bile duct was slightly dilated with parallel tubular structures, indicative of biliary ascariasis. Endoscopic retrograde cholangiopancreatography was performed under general anesthesia on 29 September 2017, and an adult Ascaris lumbricoides worm was observed. After the worm was removed from the bile duct, the patient's pain immediately subsided. The patient was successfully cured, without any complications. CONCLUSION: This report emphasizes the need for physicians to consider biliary ascariasis as a possible cause when treating cases of biliary colic.

miR-660 promotes liver cancer cell proliferation by targeting PPP2R2A.

Liver cancer (LC) is the leading cause for tumor-related death worldwide, and microRNAs (miRs) have been demonstrated to regulate the progression of LC. In the current study, the function of miR-660 in LC cells was investigated, and the results indicated that miR-660 was highly expressed in LC tissues and cells. This increased expression promoted LC cell proliferation and increased the percentage of S phase cells, while miR-660 knockdown inhibited cell proliferation and increased the percentage of G0/G1 phase cells. A Ser/Thr phosphatase protein phosphatase 2 regulatory subunit ßα (PPP2R2A) was indicated as the target of miR-660, and miR-660 could inhibit PPP2R2A levels. The luciferase reporter assay suggested that miR-660 directly bound to the 3'-untranslated region of PPP2R2A. Additionally, it was revealed that miR-660 inhibited p21 expression and promoted cyclin D1 expression, confirming that miR-660 regulated LC cell proliferation by regulating cell cycle progression. The double knockdown of miR-660 and PPP2R2A promoted LC cell proliferation, suggesting that miR-660 promoted LC proliferation by targeting PPP2R2A.

Asiatic Acid Encapsulated Exosomes of Hepatocellular Carcinoma Inhibit Epithelial-Mesenchymal Transition Through Transforming Growth Factor Beta/Smad Signaling Pathway.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in many countries, which accounts for more than 80% of primary liver cancers. Better understanding of the biology of HCC and more therapeutic strategies are urgently needed to improve the current situation. Exosomes, lipid-bound particles derived from cells, have been revealed to play versatile roles in mediating communication between tumor and its microenvironment. Thus, exosomes could act as potential drug delivery systems in cancer treatment. This study aimed to investigate the effect of asiatic acid (AA)-loaded exosomes on the proliferation and migration of HCC cells and clarify the underlying mechanisms. HCC cells were treated with AA-loaded exosomes and cell vitality, migration and invasion were examined. Compared with free AA, AA-loaded exosomes significantly reduced cell vitality, migration, invasion and epithelial mesenchymal transition (EMT). And the inhibition was enhanced as AA concentration went up. Moreover, the expression of proteins involved in EMT and TGF-ß/Smad pathway such as TGF-ß1, Smad4 and Vimentin were decreased while E-cadherin was up-regulated. Collectively, these findings demonstrate that HCC derived exosomes display as potential drug delivery vehicles in HCC treatment. And AA-loaded exosomes might work by inhibiting EMT through inactivating TGF-ß/Smad pathway.

Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p.

BACKGROUND: Previous studies indicated that long noncoding RNAs (lncRNAs) played vital roles in the development and progression of hepatocellular carcinoma (HCC). Recently, downregulation of lncRNA RP5­833A20.1 has been observed in HCC tissues. However, the underlying mechanism by which RP5­833A20.1 regulates the proliferation and apoptosis in HCC has not been investigated. Thus, this study aimed to investigate the role of RP5­833A20.1 in the progression of HCC. METHODS: The levels of RP5­833A20.1 in 30 pairs of HCC tissues and adjacent normal tissues were detected by RT-qPCR. In addition, the effects of RP5­833A20.1 on cell proliferation, apoptosis and invasion were evaluated by CCK-8, flow cytometric, transwell assays, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of RP5­833A20.1 and miR-18a-5p in HCC. RESULTS: The level of RP5­833A20.1 was significantly downregulated in HCC tissues and HCC cell lines. Downregulation of RP5­833A20.1 markedly promoted the proliferation and invasion of Bel-7402 cells. In addition, overexpression of RP5­833A20.1 notably inhibited the proliferation and invasion of Huh7 cells. Moreover, overexpression of RP5­833A20.1 obviously induced the apoptosis of Huh7 cells via increasing the levels of Bax and active caspase 3, and decreasing the levels of Bcl-2, p-Akt and p-ERK. Meanwhile, in vivo experiments performed also indicated that overexpression of RP5-833A20.1 could inhibit the tumorigenesis of subcutaneous Huh7 xenograft in nude mice. Furthermore, bioinformatics and luciferase reporter assay identified that RP5-833A20.1 functioned as a competing endogenous RNA (ceRNA) for miR-18a-5p in HCC. CONCLUSION: In this study, we found that RP5­833A20.1 was downregulated in HCC tissues. In addition, RP5-833A20.1 could suppress the tumorigenesis in HCC through inhibiting Akt/ERK pathway by acting as a ceRNA for miR-18a-5p. Therefore, RP5-833A20.1 might be a valuable and potential biomarker and therapeutic target for the treatment of HCC.

LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K/Akt signaling pathway.

The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is partially attributed to the invasive and metastatic behavior of this disease. Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, an extracellular matrix protein secreted by cultured human keratinocytes. In addition, LAMB3 is involved in the invasive and metastatic abilities of some types of cancer, including colon, pancreas, lung, cervix, stomach, and prostate cancer, but the role and mechanism of LAMB3 in PDAC have not been previously determined. Herein, we tentatively investigated the role of LAMB3 in the malignant biological behavior of PDAC. In this study, we demonstrated that LAMB3 is upregulated in PDAC. Inhibition of LAMB3 abrogated the tumorigenic outcomes of PI3K/Akt signaling pathway activation, including those involving cell cycle arrest, cell apoptosis, proliferation, invasion and migration in vitro, and tumor growth and liver metastasis in vivo. Our results showed that LAMB3 could mediate cell cycle arrest and apoptosis in PDAC cells and alter the proliferative, invasive, and metastatic behaviors of PDAC by regulating the PI3K/Akt signaling pathway. LAMB3 may be a novel therapeutic target for the treatment of PDAC in the future.