miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC

Xia, Yang; Wei, Ke; Yang, Fengming; Hu, Liu‐Qing; Pan, Chunfeng; Pan, Xinliang; Wu, Weibing; Wang, Jun; Wen, Wei; He, Zhicheng; Xu, Jing; Xu, Xinfeng; Zhu, Quan; Chen, Liang

doi:10.1038/s41419-019-1390-y

Cited by 46 publications

(33 citation statements)

References 40 publications

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“…Exosomal miR-1260b reportedly activates the Wnt/β-catenin signaling pathway in lung adenocarcinoma cells [41]. miR-1260b was suggested to directly suppress suppressor of cytokine singling 6 (SOCS6) expression and activate KIT proto-oncogene (KIT) signaling in non-small-cell lung cancer (NSCLC) [42]. KIT signaling is known to induce EMT via the KIT-MEK-ERK pathways, supporting the significant roles of miR-1260b [43].…”

Section: β-Catenin Signaling Pathwaymentioning

confidence: 85%

The Emerging Roles of Exosomes as EMT Regulators in Cancer

Kim

Lee

Shin

et al. 2020

Cells

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Epithelial–mesenchymal transition (EMT) causes epithelial cells to lose their polarity and adhesion property, and endows them with migratory and invasive properties to enable them to become mesenchymal stem cells. EMT occurs throughout embryonic development, during wound healing, and in various pathological processes, including tumor progression. Considerable research in the last few decades has revealed that EMT is invariably related to tumor aggressiveness and metastasis. Apart from the interactions between numerous intracellular signaling pathways known to regulate EMT, extracellular modulators in the tumor microenvironment also influence tumor cells to undergo EMT, with extracellular vesicles (EVs) receiving increasing attention as EMT inducers. EVs comprise exosomes and microvesicles that carry proteins, nucleic acids, lipids, and other small molecules to stimulate EMT in cells. Among EVs, exosomes have been investigated in many studies, and their role has been found to be significant with respect to regulating intercellular communications. In this review, we summarize recent studies on exosomes and their cargoes that induce cancer-associated EMT. Furthermore, we describe the possible applications of exosomes as promising therapeutic strategies.

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Section: β-Catenin Signaling Pathwaymentioning

confidence: 85%

The Emerging Roles of Exosomes as EMT Regulators in Cancer

Kim

Lee

Shin

et al. 2020

Cells

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“…YY1 is a multifunctional protein belonging to the GLI-Kruppel family that binds to other gene promoters mainly through its C-terminal zinc finger region 24,25 . YY1 is involved in the regulation of various genes that affect various biological functions of cells, including many miRNAs, such as miR-1260b 26,27 . The role YY1 plays as an oncogene or a tumor suppressor in cancers depends on the target gene that it regulates.…”

Section: Discussionmentioning

confidence: 99%

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer

Chen

Meng

et al. 2020

Cell Death Dis

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Pancreatic cancer (PC) is a malignant tumor with a poor prognosis and high mortality. However, the biological role of miR-548t-5p in PC has not been reported. In this study, we found that miR-548t-5p expression was significantly decreased in PC tissues compared with adjacent tissues, and that low miR-548t-5p expression was associated with malignant PC behavior. In addition, high miR-548t-5p expression inhibited the proliferation, migration, and invasion of PC cell lines. Regarding the molecular mechanism, the luciferase reporter gene, chromatin immunoprecipitation (ChIP), and functional recovery assays revealed that YY1 binds to the miR-548t-5p promoter and positively regulates the expression and function of miR-548t-5p. miR-548t-5p also directly regulates CXCL11 to inhibit its expression. A high level of CXCL11 was associated with worse Tumor Node Metastasis (TNM) staging in patients with PC, enhancing proliferation and metastasis in PC cells. Our study shows that the YY1/miR-548t-5p/CXCL11 axis plays an important role in PC and provides a new potential candidate for the treatment of PC.

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“…Increased miR-1260b expression has been also observed in lung cancer tissues, particularly in patients with positive lymph nodes ( 28 ). Xia Y. et al has also proved that miR-1260b promoted xenograft tumor formation in NSCLC ( 29 ). In addition, miR-1260b overexpression promoted the proliferation and invasion of hepatocellular carcinoma cells ( 30 ).…”

Section: Discussionmentioning

confidence: 98%

miR-1260b Activates Wnt Signaling by Targeting Secreted Frizzled-Related Protein 1 to Regulate Taxane Resistance in Lung Adenocarcinoma

et al. 2020

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Objectives: MicroRNAs (miRNAs) have been demonstrated to contribute to carcinogenesis; however, their association with tumor chemoresistance is not fully understood. In this study we aimed to investigate the molecular mechanisms involved in resistance to taxane-based chemotherapy in lung adenocarcinoma (LAD). Methods: We established paclitaxel-resistant A549 cells (A549/PTX) and docetaxel-resistant H1299 cells (H1299/DTX). In order to hit the mark, we employed multiple methods including qRT-PCR, western blotting analysis, loss/gain-of-function analysis, luciferase assays, drug sensitivity assays, animal experiment, wound-healing assay, and invasion assay. Results: Bioinformatics analysis and a luciferase reporter assay revealed that secreted frizzled-related protein 1 (SFRP1) is a direct target of miR-1260b. By qRT-PCR analysis, we found that miR-1260b was significantly upregulated in taxane-resistant cells as compared to parental cells. Suppression of miR-1260b reversed the chemoresistance of human LAD cells to taxanes both in vitro and in vivo, whereas ectopic miR-1260b expression decreased the sensitivity of parental LAD cell lines to taxanes. Downregulation of miR-1260b expression inactivated the Wnt signaling pathway and reversed the epithelial-mesenchymal transition (EMT) phenotype of taxane-resistant LAD cells. In clinical tumor tissue samples, high miR-1260b expression was detected in tumors of non-responding patients treated with taxane-based chemotherapy and was associated with low SFRP1 expression and poor prognosis. Conclusions: Our findings reveal that targeting of the miR-1260b/SFRP1/Wnt signaling axis might provide a novel strategy for overcoming chemotherapy resistance in LAD.

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miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC

Cited by 46 publications

References 40 publications

The Emerging Roles of Exosomes as EMT Regulators in Cancer

The Emerging Roles of Exosomes as EMT Regulators in Cancer

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer

miR-1260b Activates Wnt Signaling by Targeting Secreted Frizzled-Related Protein 1 to Regulate Taxane Resistance in Lung Adenocarcinoma

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