The protein 3-phosphoinositide-dependent protein kinase 1 (PDK1) is upregulated in cancer. Here we showed that PDK1 stimulated cell proliferation, invasion and metastasis in gallbladder cancer (GBC), by inducing JunB and epithelial–mesenchymal transition. JunB levels were increased in GBC samples and positively correlated with PDK1 levels in tumors. High levels of JunB predicted poor overall survival in GBC patients. Thus, PDK1 functions as a tumor promoter in human GBC by upregulating JunB.
Emerging evidence has shown that long non-coding RNAs (lncRNAs) play crucial roles in human cancers. However, systematic characterization of lncRNAs and their roles in gastrointestinal stromal tumor (GIST) therapy have been lacking. We performed high-throughput RNA sequencing (RNA-seq) of 20 GIST and paired adjacent normal samples. We characterized the transcriptional landscape and dysregulation of lncRNAs in GIST. We identified 866 upregulated and 1,268 downregulated lncRNAs in GIST samples, the majority of which were GIST-specific over other cancer types. Most hallmarks were found to be dysregulated in GIST samples, and lncRNAs were highly associated with cancer-related hallmarks. RP11-616M22.7 was identified to increase in imatinib-resistant samples compared to those in non-resistant samples. Further analysis revealed that RP11-616M22.7 was closely associated with the Hippo signaling pathway. By treating GIST cells with different doses of imatinib, we verified that RP11-616M22.7 knockdown promotes the sensitivity of tumor cells, whereas RP11-616M22.7 overexpression induces resistance to imatinib. We further confirmed reducing of resistance to imatinib by knocking down RP11-616M22.7 in vivo. Additionally, RP11-616M22.7 was observed to interact with RASSF1 protein.Our study revealed that deficiency of RP11-616M22.7 was able to reduce resistance of the GIST cell response to imatinib treatment both in vitro and in vivo.
BackgroundTumor-infiltrating lymphocytes (TILs) and expression of programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) are crucial for antitumor immunity. However, the status remains undetermined in HIV-infected colorectal cancer (CRC), limiting the use of immunotherapy in HIV-infected CRC patients.MethodsWe examined 27 HIV-infected patients and 120 non-HIV-infected patients with CRC from 2015-2020 at Shanghai Public Health Clinical Center. After matching the propensity score, 13 paired patients in the two groups were also compared. The expression of PD-1/PD-L1 as well as tumor-infiltrating CD4, CD8, and CD56 immune cells was examined using multiplex immunofluorescent analysis. The cell density for positive staining was calculated (cells/mm2) and compared between HIV-infected and non-HIV-infected groups. In addition, the co-expression of PD-1 on immune cells and PD-L1 on tumor cells was compared in these two groups.ResultsThe mean densities of tumor-infiltrating CD4, CD8, CD56 immune cells were 620.2, 261.2, and 0.2 cells/mm2, respectively, in HIV-infected colorectal tumors compared with 698.6, 243, and 14 cells/mm2 in non-HIV-infected tumors. PD-1 expression was 227 cells/mm2 in HIV-infected tumors and 365.2 cells/mm2 in non-HIV-infected tumors. Besides, PD-L1 expression was 108.5 cells/mm2 in HIV-infected tumors and 126.8 cells/mm2 in non-HIV-infected tumors, and no significant difference was found between the two groups. Similarly, there were no significant differences in the expression of PD-1 on TILs and PD-L1 on tumor cells.ConclusionHIV-infected CRC patients had similar tumor-infiltrating lymphocytes (CD4 and CD8 T cells) compared to non-HIV-infected controls and substantially similar PD-1 expression on TILs and PD-L1 expression on tumors. These results support the inclusion of HIV-infected CRC patients in future immunotherapy trials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.