Dataset Information

B7-H6 Promotes Cell Proliferation, Migration and Invasion of Non-Hodgkin Lymphoma via Ras/MEK/ERK Pathway Based on Quantitative Phosphoproteomics Data.

ABSTRACT: Purpose:B7 homologue 6 (B7-H6) has been found at an up-regulated level in multiple cancer cells and identified to be positively correlated with inferior clinical features. In non-Hodgkin lymphoma (NHL), however, the roles of B7-H6 and the underlying mechanism of action remain unclear. Through in vivo and in vitro experiments, the aim of this study was to explore the regulatory mechanism of B7-H6 in NHL in order to provide new therapeutic strategies that can potentially be applied in clinical practice. Methods:The expression of B7-H6 in T-lymphoblastic lymphoma (TLBL), diffuse large B cell lymphoma (DLBCL) and lymph node reactive hyperplasia (LRH) tissues were compared by immunohistochemistry. A total of 10 NHL cell lines were screened by Western blot to evaluate the expression of B7-H6. The effects of B7-H6 knockdown on cell proliferation, migration and invasion of NHL cells were studied in vivo using a transplanted tumor mice model, and in vitro by Cell Counting Kit-8 (CCK-8) and Transwell assays. Quantitative phosphoproteomics was performed to identify the changes of protein phosphorylation and related pathways affected by B7-H6. The effects of B7-H6 on NHL were validated via B7-H6 overexpression and pathway inhibitor assays. Results:The expression levels of B7-H6 in NHL cell lines, and TLBL and DLBCL tissues were significantly increased compared with those in the control groups. Inhibition of cell proliferation, migration and invasion was observed in Jurkat and Raji cells with B7-H6 knockdown. The ability of B7-H6 in promoting tumorigenesis was further validated by in vivo experiments. In addition, Ras and HIF-1 signaling pathways were shown to be significantly affected by B7-H6 through quantitative phosphorylation proteomics analysis. Ras/MEK/ERK pathway was verified to be significantly inhibited after B7-H6 knockdown by Western blot analysis. Strikingly, MEK inhibitor AZD8330 was found to have the ability to sufficiently inhibit Ras/MEK/ERK pathway, partially reverse cell proliferation and completely reverse cell migration and invasion induced by B7-H6. Conclusion:B7-H6 promotes cell proliferation, migration and invasion in NHL via Ras/MEK/ERK pathway. Hence, B7-H6 or Ras/MEK/ERK pathway targeting may be used as potential therapeutics for treating NHL.

SUBMITTER: Yang S

PROVIDER: S-EPMC7308182 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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B7-H6 Promotes Cell Proliferation, Migration and Invasion of Non-Hodgkin Lymphoma via Ras/MEK/ERK Pathway Based on Quantitative Phosphoproteomics Data.

Yang Siyuan S Yuan Lei L Wang Yanfang Y Zhu Mingxia M Wang Jing J Ke Xiaoyan X

OncoTargets and therapy 20200618

<h4>Purpose</h4>B7 homologue 6 (B7-H6) has been found at an up-regulated level in multiple cancer cells and identified to be positively correlated with inferior clinical features. In non-Hodgkin lymphoma (NHL), however, the roles of B7-H6 and the underlying mechanism of action remain unclear. Through in vivo and in vitro experiments, the aim of this study was to explore the regulatory mechanism of B7-H6 in NHL in order to provide new therapeutic strategies that can potentially be applied in clin ...[more]

PMID: 32606790

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Project description:The enhanced migratory ability of endometrial stromal cells (ESCs) is a key factor in the formation of functional endometrium‑like tissues outside the uterine cavity during endometriosis (EMS). Although accumulating evidence has suggested the importance of microRNAs (miRNAs) in the pathogenesis of EMS, the role of particular miRNAs in the invasiveness of ESCs remain poorly understood. In the present study, the function of miRNAs in the invasiveness of ESCs, along with the associated underlying mechanism involved, were investigated. Initially, the expression patterns of miRNAs in the ectopic and eutopic endometrium isolated from patients with EMS were analyzed using microarray. MicroRNA‑202‑5p (miR‑202) was selected for further study due to its previously reported suppressive effects on the invasion in various types of cancers. The expression of miR‑202 and K‑Ras in eutopic and ectopic endometrioma tissues were detected using reverse transcription‑quantitative PCR, immunohistochemistry and western blotting. The migration and invasion ability of ESCs was determined using wound healing and Transwell invasion assays, respectively. Compared with that from healthy individuals, miR‑202 expression was demonstrated to be lower in the eutopic endometrium from patients with EMS, which was even lower in ectopic endometrium. Functional experiments in primary ESCs revealed that enhanced miR‑202 expression suppressed the cell invasion and migration abilities, which was also accompanied with increased E‑cadherin and reduced N‑cadherin expression in ESCs, suggesting its potentially suppressive role in epithelial‑mesenchymal transition. K‑Ras is a well‑known regulator of the ERK signaling pathway that was shown to be directly targeted and negatively regulated by miR‑202. In addition, K‑Ras expression was found to be upregulated in the ectopic endometrium, where it correlated negatively with that of miR‑202. Knocking down K‑Ras expression mimicked the anti‑invasive effects of miR‑202 overexpression on ESCs, whilst K‑Ras overexpression attenuated the inhibitory role of miR‑202 overexpression in ESC invasion. The K‑Ras/Raf1/MEK/ERK signaling pathway was also blocked by miR‑202 overexpression. These findings suggested that miR‑202 inhibited ESC migration and invasion by inhibiting the K‑Ras/Raf1/MEK/ERK signaling pathway, rendering miR‑202 a candidate for being a therapeutic target for EMS.

Dataset Information

B7-H6 Promotes Cell Proliferation, Migration and Invasion of Non-Hodgkin Lymphoma via Ras/MEK/ERK Pathway Based on Quantitative Phosphoproteomics Data.

Publications

B7-H6 Promotes Cell Proliferation, Migration and Invasion of Non-Hodgkin Lymphoma via Ras/MEK/ERK Pathway Based on Quantitative Phosphoproteomics Data.

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