Circular RNA circTMEM59 inhibits progression of pancreatic ductal adenocarcinoma by targeting miR-147b/SOCS1: An in vitro study.

Purpose: This study aimed to detect the role and mechanism of circTMEM59 in pancreatic ductal adenocarcinoma (PDAC). Methods: 66 paired PDAC tissues and normal samples were harvested from patients diagnosed and undergoing pancreatic cancer surgery in our hospital. The expression of circTMEM59 in PDAC tissues and cell lines was detected. Based on bioinformatics information, the circTMEM59 mimics, miR-147b mimics, miR-147b inhibitor and si-suppressor of cytokine signaling 1 (SOCS1) were transfected into PDAC cells. The expression levels of circTMEM59, miR-147b and SOCS1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). RNA interaction was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell invasion and proliferation were evaluated by Transwell and Cell Counting Kit-8 (CCK-8) assays. The protein expression was detected by Western blot. Results: CircTMEM59 was confirmed to be downregulated in PDAC tumor tissues and cells. Low expression of circTMEM59 was closely correlated with the short survival time and poor clinicopathological characteristics. By up-regulating the expression of circTMEM59 in PDAC cells, cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were inhibited. More importantly, miR-147b could be sponged by circTMEM59, and knockdown of miR-147b inhibited progression of PDAC cells. Further study revealed that SOCS1 was targeted by miR-147b. SOCS1 expression was negatively related to miR-147b expression and positively related to circTMEM59 expression in PDAC tissues. Upregulated miR-147b and downregulated SOCS1 could rescue the effects of circTMEM59 on cell proliferation, EMT and invasion. Conclusion: Our data indicated that circTMEM59 inhibited cell proliferation, invasion and EMT of PDAC by regulating miR-147b/SOCS1 axis.

Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy.

BACKGROUND: Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. RESULTS: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. CONCLUSIONS: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

GHR knockdown enhances the sensitivity of HCC cells to sorafenib.

Sorafenib is approved for treatment of advanced hepatocellular carcinoma (HCC) by the Drug Administration. However, the efficacy of sorafenib has become very limited because most tumors have developed resistance to this drug. In this study, we found that sorafenib stimulated GHR expression in HCC cell lines. Thus, GHR might be linked to sorafenib resistance. To verify this hypothesis, we researched the roles of GHR knockdown and sorafenib combination in cell viability, apoptosis, cycle, and migration. The results showed that GHR blockage enhanced sorafenib blocking of cell cycle progression, leading to inhibition of this drug on HCC cell viability, and the improved promoting ability of sorafenib on cell apoptosis. In addition, it was found that GHR knockdown enhanced sorafenib inhibition of cell migration. The synergistic antitumor effects of sorafenib and GHR knockdown combination may be attributed to inhibition of PI3K/AKT/ERK1/2 signaling pathway. In conclusion, the findings suggest that GHR knockdown enhances the sensitivity of HCC cells to sorafenib. and the inactivation of PI3K/AKT/ERK1/2 signaling pathway may be the underlying mechanisms. This highlights the absence of GHR as a promising way to enhance sorafenib efficacy in HCC.