Dataset Information

TUC338 Promotes Diffuse Large B Cell Lymphoma Growth via Regulating EGFR/PI3K/AKT Signaling Pathway.

ABSTRACT: TUC338 is emerging as a novel vital long noncoding RNA (lncRNA) in human cancer; however, its role in diffuse large B cell lymphoma (DLBCL) remains unknown. In this study, we found that TUC338 was remarkably upregulated in DLBCL tissues as compared to matched normal tissues. High TUC338 was closely related to advanced Ann Arbor stage, resistance to CHOP-like treatment, and high IPI (International Prognostic Index). Stable knockdown of TUC338 evidently inhibited cell proliferation and chemotherapy resistance to Adriamycin and induced apoptosis. Further, we found that TUC338 was able to directly bind to miR-28-5p and increased EGFR level, resulting in activating carcinogenic PI3K/AKT signaling, thereby facilitating DLBCL uncontrolled growth. Moreover, we also found that depletion of TUC338 led to the inactivation of EGFR/PI3K/AKT pathway in vivo by using the xenograft tumor model. Preclinically, DLBCL patients with high TUC338 had shorter survival time than those with low TUC338, and serum TUC338 level was identified as an excellent indicator for DLBCL diagnosis. In sum, our findings clearly indicate that TUC338 functions as an oncogenic lncRNA in DLBCL through activating EGFR/PI3K/AKT pathway via sponging and inhibiting miR-28-5p, which may be a promising target for DLBCL treatment.

SUBMITTER: Li Y

PROVIDER: S-EPMC8079195 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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TUC338 Promotes Diffuse Large B Cell Lymphoma Growth via Regulating EGFR/PI3K/AKT Signaling Pathway.

Li Yan Y Li Yan Y Jia Zhenwei Z Zhao Hongbo H Liu Xiaoyan X Luo Jianmin J Cui Guirong G Kong Xiaoyang X

Journal of oncology 20210419

TUC338 is emerging as a novel vital long noncoding RNA (lncRNA) in human cancer; however, its role in diffuse large B cell lymphoma (DLBCL) remains unknown. In this study, we found that TUC338 was remarkably upregulated in DLBCL tissues as compared to matched normal tissues. High TUC338 was closely related to advanced Ann Arbor stage, resistance to CHOP-like treatment, and high IPI (International Prognostic Index). Stable knockdown of TUC338 evidently inhibited cell proliferation and chemotherap ...[more]

PMID: 33986803

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Project description:BackgroundSirtuin 6 (Sirt6) is a highly conserved ADP-ribosylase and NAD+ dependent deacylase, involved in broad cellular processes. This molecule possesses contradictory roles in carcinogenesis, as it has been documented to both suppressing and augmenting tumor growth. This project aimed to explore the expression and functions of Sirt6 in diffuse large B-cell lymphoma (DLBCL), especially with regards to the regulatory role of OSS_128167, a novel small molecular inhibitor targeting Sirt6.MethodsImmunohistochemistry (IHC) was conducted to assess the expression of Sirt6 on paraffin-embedded tissues. Microarray dataset GSE32918 and GSE83632 were obtained from Gene Expression Omnibus and survival analysis was performed. Lentivirus vectors either encoding shSirt6, lvSirt6 or empty lentiviral vector were stably transfected into DLBCL cells. LY1 cell transfected with shSirt6 were performed RNA-sequencing (RNA-seq) analysis, functional enrichment analyses of gene ontology (GO) and gene set enrichment analysis (GSEA). DLBCL cells were subcutaneously injected to SCID beige mice to establish xenograft models.ResultsSirt6 is found to be overexpressed in DLBCL, and is related to poor prognosis. Sirt6-deprived DLBCL cells displayed augmented sensitivity towards chemotherapy, higher rates of apoptosis, dysfunctional cell proliferation, and arrested cell cycle progression between the G2 and M phases. Selective OSS_128167-mediated Sirt6 blockage resulted in similar anti-lymphoma effects when compared to Sirt6 knocked-down DLBCL cells. PI3K signaling along with phosphorylation of its downstream targets was reduced upon Sirt6 downregulation. Xenograft models subjected to either OSS_128167 treatment or Sirt6-knockdown showed suppressed tumor growth and lower Ki-67 level.ConclusionsThese findings provide mechanistic insights into the oncogenic activity of Sirt6 in DLBCL for the first time and highlighted the potency of OSS_128167 for novel therapeutic strategies in DLBCL.

Dataset Information

TUC338 Promotes Diffuse Large B Cell Lymphoma Growth via Regulating EGFR/PI3K/AKT Signaling Pathway.

Publications

TUC338 Promotes Diffuse Large B Cell Lymphoma Growth via Regulating EGFR/PI3K/AKT Signaling Pathway.

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