ABSTRACT
@# Chimeric antigen receptor (CAR) T lymphocyte has shown attractive prospects in the treatment of lymphohematopoietic malignancies including B-cell lymphoblastic leukemia, B-cell lymphoma and multiple myeloma. Many applicants have submitted investigational new drug (IND) applications to Center for Drug Evaluation of National Medical Products Ggency, however, many of the INDs have problems in patient selection, prognostic indicators and risk management, etc, which might hinder the evaluation of the safety and efficacy of CAR-T cells. Thus, we made some suggestions on the above-mentioned problems through summarizing clinical experience and communicating with domestic clinical experts, which the sponsors and researchers can refer to when conducting CAR-T cell clinical trials for registration.
ABSTRACT
@# Objective: To investigate the mechanism of lncRNA XIST (XIST) on modulating gastric cancer progression via regulating miR-337-3p/HOXC8 axis. Methods: A total of 58 cases of gastric cancer tissues and corresponding para-cancerous tissues resected from March 2013 to January 2018 in Department of General Surgery, Kailuan General Hospital of Tangshan City were collected for this study; in addition, human gastric cancer cell lines (AGS, MGC803, HGC27) and human gastric mucosal GES-1 cells were also collected. qPCR was used to detect the expressions of XIST and miR-337-3p in above mentioned gastric tissues and cell lines. XIST-knockdown vectors, miR-337-3p mimics, miR-337-3p inhibitor and HOXC8-overexpression vectors were transfected into AGS cells. The proliferation and invasion of AGS cells were detected by CCK-8 and Transwell experiments respectively, and the expression levels of HOXC8, E-cadherin, N-cadherin and vimentin were detected by WB. The targeting relationships between XIST, miR337-3p and HOXC8 were verified by dual-luciferase reporter gene assay. Results: XIST was up-regulated in gastric cancer tissues and cell lines (all P<0.01). XIST knockdown significantly inhibited proliferation, invasion and EMT of AGS cells (P<0.05 or P<0.01). Moreover, XIST directly interacted with miR-337-3p and down-regulated its expression, while HOXC8 was the target gene of miR-3373p. Furthermore, XIST knockdown suppressed proliferation, invasion and EMT ofAGS cells through up-regulating the inhibitory effect of miR-337-3p on HOXC8 (P<0.05 or P<0.01). Conclusion: XIST knockdown can suppress the proliferation, invasion and EMT of AGS cells, which may be related with down-regulation of HOXC8 by targeting miR-337-3p.