microRNA‑196a‑3p inhibits cell proliferation and promotes cell apoptosis by targeting ADP ribosylation factor 4 in diffuse large B‑cell lymphoma

Fu,Jianhong; Lou,Xiaoli; Wan,Shan; Zhao,Xin; Chen,Zhi; Zhu,Minsheng; Guo,Lingchuan; Wu,Depei; Wang,Shouli

doi:10.3892/or.2020.7901

microRNA‑196a‑3p inhibits cell proliferation and promotes cell apoptosis by targeting ADP ribosylation factor 4 in diffuse large B‑cell lymphoma

Authors:
- Jianhong Fu
- Xiaoli Lou
- Shan Wan
- Xin Zhao
- Zhi Chen
- Minsheng Zhu
- Lingchuan Guo
- Depei Wu
- Shouli Wang
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Affiliations: Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: December 16, 2020 https://doi.org/10.3892/or.2020.7901
Pages: 764-775

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Abstract

Diffuse large B‑cell lymphoma (DLBCL) is the most prevalent type of non‑Hodgkin's lymphoma with a heterogeneous molecular pathogenesis and aggressive clinical manifestations. The aim of the present study was to investigate the role of miR‑196a‑3p and its target gene in the development and progression of DLBCL. RT‑qPCR was used to detect the miR‑196a‑3p expression level in human DLBCL cell lines and DLBCL pathological tissues and compare them with the normal control. The clinical significance of the miR‑196a‑3p expression was also analyzed in DLBCL patients. Next, the effect of miR‑196a‑3p overexpression on the cell cycle, apoptosis, and proliferation of DLBCL cells was evaluated. To explore its underlying mechanism, the target gene of miR‑196a‑3p was predicted and validated using bioinformatics and molecular biological approaches. Finally, the expression of this target gene in clinical specimens and its correlation with clinicopathological characteristics were determined. The decreased expression of miR‑196a‑3p was validated in DLBCL, with further analysis proving that it was correlated with poor prognosis. It was shown that the overexpression of miR‑196a‑3p was associated with cell cycle arrest, enhanced apoptosis, and inhibited proliferation in DLBCL cells. Furthermore, ADP ribosylation factor 4 (ARF4) was verified as the downstream target gene of miR‑196a‑3p. Similar to miR‑196a‑3p restoration in vitro, endogenous ARF4‑knockdown was proven to inhibit cell proliferation through cell cycle arrest and elevate apoptosis in DLBCL. The present results indicated that miR‑196a‑3p downregulation contributed to the tumorigenesis of DLBCL by targeting ARF4 expression, which may be used as a novel prognostic marker or potential molecular therapeutic target for DLBCL management in the future.

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