Long noncoding RNA DANCR promotes nasopharyngeal carcinoma progression by interacting with STAT3, enhancing IL-6/JAK1/STAT3 signaling

Zhang, Xixia; Yang, Jing; Bian, Zhigang; Shi, Dong; Cao, Zhigang

doi:10.1016/j.biopha.2019.108713

Cited by 30 publications

(27 citation statements)

References 26 publications

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“…20 DANCR interacts with STAT3 to activate STAT3 in NPC cells. 40 Here, we also showed that DANCR could activate IL-6/ STAT3 signaling through the upregulation of PSMD10. Interestingly, activation of IL-6/STAT3 signaling promoted DANCR transcription reciprocally, indicating a positive regulatory feedback loop between DANCR and IL-6/STAT3 signaling pathway.…”

Section: Discussionsupporting

confidence: 53%

<p>LncRNA DANCR Promotes Sorafenib Resistance via Activation of IL-6/STAT3 Signaling in Hepatocellular Carcinoma Cells</p>

Liu¹,

Chen²,

Yuan³

et al. 2020

OTT

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Background: Hepatocellular carcinoma (HCC) is one of the major malignancies and the second most common cause of cancer-related death worldwide. Sorafenib, an approved first-line systematic treatment agent for HCC, is capable to effectively improve the survival of patients with advanced HCC. The long-noncoding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) has been reported to exert oncogenic functions in several kinds of human cancers. However, the role of lncRNA DANCR in sorafenib resistance in HCC remains unknown. Methods: The expression levels of DANCR in HCC tissues were detected by qRT-PCR. DANCR overexpression and knockdown models were established and utilized to investigate the functional role of DANCR on sorafenib resistance in HCC cells. The MS2-binding sequences-MS2-binding protein-based RNA immunoprecipitation assay, RNA pull-down and luciferase reporter assay was used to detect the association between DANCR and PSMD10 mRNA. The activation of DANCR transcription mediated by STAT3 was assessed by luciferase reporter and chromatin immunoprecipitation assays. Results: We found that DANCR was significantly overexpressed in HCC tissues and associated with prognosis of HCC patients. Overexpression and knockdown experiments demonstrated that DANCR promoted sorafenib resistance in HCC cells in vitro and in vivo. Mechanistically, the role of DANCR relied largely on the association with PSMD10. DANCR stabilized PSMD10 mRNA through blocking the repressing effect of several microRNAs on PSMD10. Besides, DANCR activated IL-6/STAT3 signaling via PSMD10. Furthermore, we revealed that DANCR transcription was enhanced by the activation of IL-6/ STAT3 signaling, indicating a positive feedback loop of DANCR and IL-6/STAT3 signaling. Conclusion: Collectively, our study is the first to elucidate the mechanism of DANCRmediated sorafenib resistance via PSMD10-IL-6/STAT3 signaling axis, which provides a promising target for developing new therapeutic strategy for sorafenib tolerance of HCC.

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Section: Discussionsupporting

confidence: 53%

<p>LncRNA DANCR Promotes Sorafenib Resistance via Activation of IL-6/STAT3 Signaling in Hepatocellular Carcinoma Cells</p>

Liu¹,

Chen²,

Yuan³

et al. 2020

OTT

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“…Previously, several studies have implicated the potential role of IL-6 in the pathogenesis and progression of NPC. For instance, IL-6 has been shown to promote proliferation and invasion of NPC cells through STAT3 signaling [12,30]. Sun et al reported that IL-6 promoted migration and invasion of HNE1 and CNE1-LMP1 NPC cells by upregulating MMP-2 and MMP-9 expression [31].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that IL-6 enhances resistance of a variety of cancers to cisplatin (DDP) treatment via activating STAT3 pathway [29][30][31][32][33][34][35].…”

Section: Exogenous and Msc-derived Il-6 Promotes Resistance Of Npc Cementioning

confidence: 99%

Mesenchymal stem/stromal cells-derived IL-6 promotes nasopharyngeal carcinoma growth and resistance to cisplatin via upregulating CD73 expression

Zeng

Chen

et al. 2020

J. Cancer

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Previous studies have implicated the important role of mesenchymal stem/stromal cells (MSCs) within tumor microenvironment (TME) in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), but the potential mechanisms are still unclear. Herein, we showed that an elevated IL-6 level was positively correlated with elevated expression of CD73 in TME of NPC. NPC specimens with an IL-6 high CD73 high phenotype showed higher expression levels of gp80, gp130, p-STAT3, MMP-9 and α-SMA, and clinically, a poorer prognosis than those with an IL-6 low CD73 low phenotype. We found that stimulation with conditioned media derived from IL-6 gene knocked out MSC (MSC IL6KO-CM) down-regulated the expression of CD73, IL-6, gp80, p-STAT3, and proliferative cell nuclear antigen (PCNA) in CNE-2 NPC cells. Meanwhile, NPC cells co-cultured with MSC IL6KO-CM were more sensitive to cisplatin than those co-cultured with MSC-CM. Additionally, MSC-derived IL-6 transcriptionally upregulated CD73 expression via activating STAT3 signaling pathway in NPC cells. In summary, our findings suggest that MSCs promote NPC progression and chemoresistance by upregulation of CD73 expression via activating STAT3 signaling pathway.

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“…IL‐6 acts directly on tumor cells and induces the expression of STAT3 target genes, which then encode proteins that drive tumor cell proliferation and/or survival . The IL‐6/STAT3 signaling pathway is abnormally activated in diverse tumors, such as nasopharyngeal carcinoma, breast cancer, and ESCC . Comparatively, the mechanism that causes abnormal activation of IL‐6/STAT3 in ESCC needs further investigation.…”

Section: Introductionmentioning

confidence: 99%

“…24 The IL-6/STAT3 signaling pathway is abnormally activated in diverse tumors, such as nasopharyngeal carcinoma, breast cancer, and ESCC. [25][26][27] Comparatively, the mechanism that causes abnormal activation of IL-6/STAT3 in ESCC needs further investigation.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Xu¹,

Xiaojing²,

Li³

et al. 2019

IUBMB Life

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Circular RNAs (circRNAs) are novel noncoding RNAs (ncRNAs) with covalently closed‐loop structures that play an essential regulatory role in diverse malignancies, including esophageal squamous cell cancer (ESCC). Circ_0000654 expression in ESCC and its mechanism of action remains unclear. Real‐time PCR (RT‐PCR) was employed to detect circ_0000654 and miR‐149‐5p expression in ESCC tissues. Circ_0000654 and miR‐149‐5p expression in ESCC cells was selectively regulated. Furthermore, interleukin 6 (IL‐6) and signal transducer and activator of transcription 3 (STAT3) expression in cells was detected by RT‐PCR and western blot analysis, while CCK8, BrdU, flow cytometry, and transwell assays were used to monitor cell proliferation, apoptosis, migration and invasion, respectively. The dual‐luciferase reporter assay and RIP assay were used to verify the targeting relationship between circ_0000654 and miR‐149‐5p, miR‐149‐5p and IL‐6. The function of circ_0000654 on ESCC cell proliferation and metastasis in vivo was examined using a subcutaneous xenograft model and a tail intravenous injection model in nude mice. Circ_0000654 was significantly upregulated in ESCC tissues and cell lines, and its high expression was remarkably associated with an increased T stage and local lymph node metastasis in ESCC patients. Circ_0000654 overexpression and knockdown experiments revealed that circ_0000654 regulated ESCC cell proliferation, migration, invasion, and apoptosis in vitro. Circ_0000654 was identified as a sponge of miR‐149‐5p and facilitated ESCC progression by indirectly activating the IL‐6/STAT3 signaling pathway. Additionally, knocking down circ_0000654 strikingly repressed ESCC growth and metastasis in vivo. In summary, circ_0000654 functions as an oncogenic circRNA in ESCC and accelerates ESCC progression via adsorbing miR‐149‐5p and activating the IL‐6/STAT3 signaling pathway.

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Long noncoding RNA DANCR promotes nasopharyngeal carcinoma progression by interacting with STAT3, enhancing IL-6/JAK1/STAT3 signaling

Cited by 30 publications

References 26 publications

<p>LncRNA DANCR Promotes Sorafenib Resistance via Activation of IL-6/STAT3 Signaling in Hepatocellular Carcinoma Cells</p>

<p>LncRNA DANCR Promotes Sorafenib Resistance via Activation of IL-6/STAT3 Signaling in Hepatocellular Carcinoma Cells</p>

Mesenchymal stem/stromal cells-derived IL-6 promotes nasopharyngeal carcinoma growth and resistance to cisplatin via upregulating CD73 expression

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

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