RNF7 Facilitated the Tumorigenesis of Pancreatic Cancer by Activating PI3K/Akt Signaling Pathway.

RING finger protein-7 (RNF7) functions as a positive regulator in the progression of multiple malignancies. However, the underlying mechanism by which RNF7 contributes to pancreatic cancer (PC) is lacking. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the level of RNF7expression in PC cell lines and tissues. The role of RNF7 in PC tumorigenesis was analyzed by Cell Counting Kit-8 (CCK-8). 5-Ethynyl-20-deoxyuridine (EdU), wound-healing/Transwell assays, as well as a subcutaneous tumorigenesis model were constructed to assess the role of RNF7 in PC cells. The association between RNF7 and PI3K/Akt signaling were assessed by western blot and further confirmed by rescue experiments. The PC patients with upregulated expression of RNF7 had poor survival. Overexpression of RNF7 significantly facilitated PC proliferative and migrative and invasive properties in vitro and vivo; however, knockdown of RNF7exhibited the opposite results. Mechanistically, RNF7 promoted PANC-1 and SW1990 cell growth through impacting the activation of the PI3K/Akt signaling pathway. Our data demonstrated that RNF7 promoted PC tumorigenesis via activating the PI3K/Akt signaling pathway and might be regarded as one of the potential therapies to PC.

High expression of syndecan-4 is related to clinicopathological features and poor prognosis of pancreatic adenocarcinoma.

OBJECTIVE: Pancreatic adenocarcinoma (PAAD) is a leading cause of cancer-related mortality in adults. Syndecan-4 (SDC4) is involved in cancer pathogenesis. Therefore, this study aimed to explore the expression and clinical significance of SDC4 in PAAD. METHODS: Differentially expressed genes (DEGs) between PAAD and normal pancreas were screened from the GTEx and TCGA databases, and the correlationship between the DEGs and prognosis were analyzed. The prognostic value of the screened SDC4, SERPINE1, and SLC2A1 was evaluated using the Kaplan-Meier curve and SDC4 was subsequently selected as the better candidate. Also, SDC4 expression was analyzed in PAAD tissues, the other risk factors affecting postoperative survival were analyzed using Cox regression analysis, and SDC4-mediated pathways enrichment was identified by GSVA and GSEA. SDC4 expression in PAAD tissues and adjacent normal tissues of selected PAAD patients was detected by RT-qPCR and immunohistochemistry. The correlation between SDC4 and clinical features was evaluated by the χ2 test. RESULTS: SDC4 was highly expressed in PAAD tissues. Elevated SDC4 was correlated with reduced overall survival. SDC4 enrichment pathways included spliceosome function, proteasome activity, pentose phosphate pathway, base excision repair, mismatch repair, DNA replication, oxidative phosphorylation, mitotic spindle formation, epithelial-mesenchymal transition, and G2M checkpoints. SDC4 was elevated in PAAD tissues of PAAD patients compared with adjacent normal tissues. High SDC4 expression was related to metastatic differentiation, TNM stage, lymphatic metastasis, and lower 3-year survival rate. SDC4 was an independent risk factor affecting postoperative survival. CONCLUSION: SDC4 was highly expressed in PAAD and was related to clinicopathological features and poor prognosis, which might be an important index for PAAD early diagnosis and prognosis.

circACTG1 Promotes Hepatocellular Carcinoma Progression by Regulating miR-940/RIF1 Axis and Activating AKT/mTOR Pathway.

Background: Hepatocellular carcinoma (HCC) is recognized as the fourth in incidence and the third in mortality worldwide. The onset of HCC is insidious and often asymptomatic at the early stage. HCC is more prone to metastasis, recurrence, and drug resistance than other solid tumors owing to its feature of high heterogeneity. Therefore, what particularly important is to search for effective molecular markers in the occurrence and progression of HCC. Aim: To probe into the therapeutic potential of circACTG1 (hsa_circ_0046144) in HCC cell migration and invasion, providing a new insight and molecular target to diagnose and cure HCC patients. Methods: The circACTG1 expression in collected HCC cells was determined by quantitative polymerase chain reaction (qPCR). Assessment for circACTG1 diagnosing capability was analyzed by receiver operating characteristic (ROC) curves. Transwell assay, wound healing assay, and cell counting kit-8 assay were used for monitoring the effect of circACTG1 in HCC cell invasion, migration, and proliferation, respectively; qPCR, luciferase reporter assay, databases, and Western blot analysis were used for identifying the modulation mechanisms among circACTG1, miRNA-940, and RIF1. What is more, our study verified AKT-mTOR signaling after miR-940 mimic treatment or circACTG1 knockdown. Results: circACTG1 was overexpressed in HCC cells and tissues. Knockdown of circACTG1 restrained 97H and Huh7 cell migration and invasion. Significantly, circACTG1 was discovered to serve as a miR-940 sponge. miR-940 activation rebated the circACTG1 level, and conversely, miR-940 inhibition boosted the circACTG1 level. However, this effect or relationship was not seen after circACTG1 mutation. Furtherly, miR-940-downregulated expression was also found in HCC patients, and importantly, miR-940 inhibition reversed circACTG1 expression in 97H cells with circACTG1 knockdown. Moreover, the expression of RIF1 was significantly reduced after inhibiting circACTG1 or overexpressing miR-940 but rescued when both circACTG1 and miR-940 were inhibited. Finally, circACTG1 and miR-940 played significant roles of regulating AKT-mTOR signaling. Conclusion: circACTG1 expression remarkably ascended in HCC, which is of certain diagnostic value. Moreover, circACTG1 potentially regulates HCC cell proliferation, invasion, and migration via miR-940/RIF1/AKT/mTOR pathway.

Prodigiosin inhibits cholangiocarcinoma cell proliferation and induces apoptosis via suppressing SNAREs-dependent autophagy.

BACKGROUND: Prodigiosin (PG), a natural red pigment produced by numerous bacterial species, has been a eye-catching research point in recent years for its anticancer activity. However, the role of PG in the cancer biology of cholangiocarcinoma (CCA) remains vague. METHODS: The proliferation of CCA cells was detected by Cell Counting Kit-8(CCK-8), Colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was evaluated by flow cytometry assay and western blot assay. The effects of PG or SNAREs on cell autophagy were measured by autophagy flux assay and western blot assay. Xenograft mouse models were used to assess the role of PG in CCA cells in vivo. RESULTS: PG could inhibit the proliferation and viability of CCA cells in a concentration- and time-dependent manner via suppressing the late stage of autophagy. Mechanistically, PG inhibits the fusion of autophagosomes and lysosomes by blocking STX17 and SNAP29, components of soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs)complex. When STX17 and SNAP29 were overexpressed, the inhibitory effect of PG on CCA cells autophagy was relieved. In addition, PG showed obvious inhibitory effects on cancer cell viability but no toxic effects on organs in xenotransplantation models. CONCLUSION: Taken together, our results demonstrated that PG inhibits CCA cell proliferation via suppressing SNAREs-dependent autophagy, implying that PG could be a potential chemotherapy drug for advanced CCA.

Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. HCC cells possess biological characteristics of high invasion and metastasis. In this respect, to prevent cancer cell invasion and metastasis and early active intervention, we herein screened through the TCGA database for further prognostic analysis including overall survival and disease-free survival . The Kaplan-Meier curve suggested that Cyclin-Dependent Kinase 4 (CDK4) might be an independent prognostic factor for HCC. Moreover, we performed mRNA expression analysis to measure CDK4 levels in normal liver tissues and HCC tissues, and immunohistochemistry analysis to detect protein level of CDK4 in Non-tumor tissue and HCC tissues . Our findings indicated that the expression of CDK4 was significantly higher in tumor tissues compared with Non-tumor tissue in HCC, which increased from HCC stage 1 to 3. Furthermore, the results of transwell-assay indicated that knocking down CDK4 significantly suppresses the invasion and migration of HCC cells, and the results of bioinformatics analysis revealed that genes closely associated with CDK4 are potentially worthy of further investigation. Additionally, the results of Western Blot indicated CDK4 regulates epithelial mesenchymal transition in HCC,and CDK4 appears to regulate EMT and HCC progression via the Wnt/ß-catenin pathway. Collectively, this study found the key target gene through bioinformatic analysis and further functional validation through cell experiments. In particular, CDK4 is anticipated to become a crucial hub gene to snipe the metastasis of cancer cells in HCC.Abbreviations: Hepatocellular carcinoma (HCC);Cyclin-Dependent Kinase 4(CDK4);Genomic Data Commons (GDC); genes; EC, Endometrial cancer; GEO, gene expression omnibus; GO, Gene Ontology; GSEA, Gene set enrichment analysis; KEGG, Database; TCGA, The Cancer Genome Atlas; TSGs, tumor suppressor genes;epithelial mesenchymal transition (EMT).

Retroperitoneal Spindle Cell Tumor: A Case Report.

Spindle cell tumor is very rare. Herein, we report a case of retroperitoneal spindle cell tumor in a 52-year-old female. The patient first presented with a complaint of persistent pain in the right upper abdomen. In the follow-up, a CT scan was performed and showed a retroperitoneal soft tissue density mass measuring 11 cm in diameter. Then, a subsequent operation was performed, and we completely removed the tumor and partially invaded lesions. The tumor was histologically diagnosed as a spindle cell tumor. Therefore, it is imperative for us to enhance the understanding of this seldom found tumor. Surgery remains the best option for treatment.