Potential of the tumor‑derived extracellular vesicles carrying the miR‑125b‑5p target TNFAIP3 in reducing the sensitivity of diffuse large B cell lymphoma to rituximab

Zhang, Li; Zhou, Shunhua; Zhou, Tiejun; Li, Xiaoming; Tang, Junling

doi:10.3892/ijo.2021.5211

Cited by 15 publications

(11 citation statements)

References 43 publications

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“…NFκB interacts with the corresponding DNA sites, which can regulate the expression of related target genes (such as TNFAIP3 protein). The TNFAIP3 protein then inhibits the phosphorylation of IκB via multiple different mechanisms, 6 Disease Markers thereby increasing the IκB content, which in turn inhibits NFκB activity [6,7]. This experimental study revealed that the NFκB protein expression was vastly increased in CRC cells and significantly lower in normal adjacent tissues.…”

Section: Discussionmentioning

confidence: 75%

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Clinical and Basic Evaluation of the Effects of Upregulated TNFAIP3 Expression on Colorectal Cancer

Ren

Zhang

et al. 2022

Disease Markers

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Objective. To assess the TNFAIP3 and nuclear factor κB (NFκB) protein expressions in colorectal cancer (CRC) tissue and to analyze the association of these proteins with the clinical pathological characteristics of CRC. Methods. The following methods should be used in clinical trials: information collection and immunohistochemical methods. The following methods are used for cell experiment: cell transfection, CCK8 detection method, transwell experiment, and western blot experiment. Explore the TNFAIP3 expression in CRC cells, and assess the effect of upregulated TNFAIP3 expression on CRC cell proliferation, invasion, and migration. In clinical experiment, we selected the tumor tissues of 39 CRC patients as our experimental samples. We also collected corresponding patient demographics, such as sex, age, cell differentiation, tumor type, and lymph node metastasis. We also analyzed the TNFAIP3 and NFκB protein expressions in 20 experimental and 20 control samples and evaluated potential correlations between these two proteins and clinical pathological characteristics of CRC. For basic experiment, we established CRC cell lines with elevated TNFAIP3 expression and then randomly divided the cells into three groups, namely, TNFAIP3, NS, and Con groups. Using the transwell and CCK8 methods, we detected the CRC migration abilities and cell proliferation, respectively. We also employed western blot analysis to assess protein expression in the three groups. Results. NFκB was highly expressed, and TNFAIP3 was scarcely expressed in the experimental group versus control. The expression of both these proteins were strongly related to the degree of tumor differentiation ( P < 0.05 ). The TNFAIP3 and NFκB protein expressions were significantly associated with lymph node metastasis and tumor differentiation ( P < 0.05 ). For basic experiment, compared to the Con and NS groups, TNFAIP3 protein expression levels, cell proliferation, invasion, and migration were significantly increased in the TNFAIP3 group ( P < 0.05 ). Conclusion. TNFAIP3 overexpression strongly inhibited CRC proliferation, invasion, and migration. Enhanced NFκB protein expression in CRC tissues was associated with elevated malignant degree, metastasis, and TNFAIP3 protein expression in patients who demonstrated high malignant degree and metastasis. Our evidences suggest the promising potential of utilizing TNFAIP3 and NFκB as important reference indices for determining the prognostic outcome of CRC. Furthermore, we revealed that TNFAIP3 overexpression inhibited CRC cell proliferation, invasion, and migration.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Clinical and Basic Evaluation of the Effects of Upregulated TNFAIP3 Expression on Colorectal Cancer

Ren

Zhang

et al. 2022

Disease Markers

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“…Exosomal miR-7-5p and miR-425-5p, derived from bone marrow mesenchymal stem cells (BM-MSCs), were confirmed to inhibit proliferation, and promote apoptosis of AML cells by targeting PI3K/AKT/mTOR signaling pathway and Wilms tumor 1-associated protein (WTAP), respectively [ 209 , 210 ]. Exosomal miR-125-5p reduced sensitivity of DLBCL cells to rituximab treatment [ 211 ], while increased levels of exosomal miR-99a-5p and miR-125b-5p in sera samples of DLBCL patients were associated with shorter PFS data [ 212 ]. In MM patients, down-regulation of four exosomal miRNAs (miR-5a-5p, miR-16-5p, miR-17-5p and miR-20a-5p) was registered in the bortezomib resistance group [ 207 ], and high levels of exosomal miR-1305 indicated poor OS [ 213 ].…”

Section: Clinical Applications Of Mirnas Focusing On Hematological Ma...mentioning

confidence: 99%

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

Gaál

2022

IJMS

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MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs, that are involved in the multistep process of carcinogenesis, contributing to all established hallmarks of cancer. In this review, implications of miRNAs in hematological malignancies and their clinical utilization fields are discussed. As components of the complex regulatory network of gene expression, influenced by the tissue microenvironment and epigenetic modifiers, miRNAs are “micromanagers” of all physiological processes including the regulation of hematopoiesis and metabolic pathways. Dysregulated miRNA expression levels contribute to both the initiation and progression of acute leukemias, the metabolic reprogramming of malignantly transformed hematopoietic precursors, and to the development of chemoresistance. Since they are highly stable and can be easily quantified in body fluids and tissue specimens, miRNAs are promising biomarkers for the early detection of hematological malignancies. Besides novel opportunities for differential diagnosis, miRNAs can contribute to advanced chemoresistance prediction and prognostic stratification of acute leukemias. Synthetic oligonucleotides and delivery vehicles aim the therapeutic modulation of miRNA expression levels. However, major challenges such as efficient delivery to specific locations, differences of miRNA expression patterns between pediatric and adult hematological malignancies, and potential side effects of miRNA-based therapies should be considered.

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“…This model would explain the clinical efficacy of Brentuximab vedotin also in cases of lack of the targeting antigen on tumor cells. In the same way, DLBCL EVs carrying miR-125b-5p can reduce tumor sensitivity to rituximab by inhibiting TNFAIP3 expression and reducing CD20 expression ( 117 ). Whether the miR-125b-5p/TNFAIP3 axis can be used as a therapeutic approach for increasing DLBCL sensitivity to anti-CD20 antibodies requires further investigations.…”

Section: Disrupting the Ev “Remote Communication” To Improve Lymphoma Prognosismentioning

confidence: 99%

Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

Dumontet¹,

Mancini²,

Tarte

2021

Front. Immunol.

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B-cell non-Hodgkin lymphoma (B-NHL) evolution and treatment are complicated by a high prevalence of relapses primarily due to the ability of malignant B cells to interact with tumor-supportive lymph node (LN) and bone marrow (BM) microenvironments. In particular, progressive alterations of BM stromal cells sustain the survival, proliferation, and drug resistance of tumor B cells during diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The current review describes how the crosstalk between BM stromal cells and lymphoma tumor cells triggers the establishment of the tumor supportive niche. DLBCL, FL, and CLL display distinct patterns of BM involvement, but in each case tumor-infiltrating stromal cells, corresponding to cancer-associated fibroblasts, exhibit specific phenotypic and functional features promoting the recruitment, adhesion, and survival of tumor cells. Tumor cell-derived extracellular vesicles have been recently proposed as playing a central role in triggering initial induction of tumor-supportive niches, notably within the BM. Finally, the disruption of the BM stroma reprogramming emerges as a promising therapeutic option in B-cell lymphomas. Targeting the crosstalk between BM stromal cells and malignant B cells, either through the inhibition of stroma-derived B-cell growth factors or through the mobilization of clonal B cells outside their supportive BM niche, should in particular be further evaluated as a way to avoid relapses by abrogating resistance niches.

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Potential of the tumor‑derived extracellular vesicles carrying the miR‑125b‑5p target TNFAIP3 in reducing the sensitivity of diffuse large B cell lymphoma to rituximab

Cited by 15 publications

References 43 publications

Clinical and Basic Evaluation of the Effects of Upregulated TNFAIP3 Expression on Colorectal Cancer

Clinical and Basic Evaluation of the Effects of Upregulated TNFAIP3 Expression on Colorectal Cancer

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

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