hsa-MicroRNA-28-5p Inhibits Diffuse Large B-Cell Lymphoma Cell Proliferation by Downregulating 14-3-3 ζ Expression

Shufang Yan; Yang Chen; Meihong Yang; Qian Zhang; Jiajia Ma; Bo Liu; Liuqing Yang; Xinxia Li

doi:10.1155/2022/4605329

hsa-MicroRNA-28-5p Inhibits Diffuse Large B-Cell Lymphoma Cell Proliferation by Downregulating 14-3-3 ζ Expression

Evid Based Complement Alternat Med. 2022 Jan 4:2022:4605329. doi: 10.1155/2022/4605329. eCollection 2022.

Authors

Shufang Yan^{1

2}, Yang Chen³, Meihong Yang^{1

2}, Qian Zhang^{1

2}, Jiajia Ma^{1

2}, Bo Liu^{1

2}, Liuqing Yang^{1

2}, Xinxia Li¹

Affiliations

¹ Department of Pathology, The Tumor Hospital, Affiliated to Xinjiang Medical University, Xinjiang 830011, China.
² Xinjiang Medical University, Xinjiang 830011, China.
³ Department of Orthopedics, The First Affiliated Hospital of Tsinghua University, Beijing Huaxin Hospital, Beijing 100016, China.

Abstract

MicroRNAs (miRNAs) participate in the comprehensive biological process of several cancer types. In our former study, we found that hsa-microRNA- (miR-)28-5p was downregulated, but tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activating protein zeta (14-3-3ζ or YWHAZ) was upregulated in diffuse large B-cell lymphoma (DLBCL) tissues. We predicted that YWHAZ was a target gene for hsa-miR- 28-5p using bioinformatics analysis. Our goal was to reveal the role of hsa-miR-28-5p in DLBCL. YWHAZ was tested by immunohistochemistry (IHC) in formalin-fixed paraffin-embedded (FFPE) tissues of 137 DLBCL tissues, and the expression of hsa-miR-28-5p and YWHAZ was examined by quantitative real-time polymerase chain reaction (qRT-PCR) in 15 fresh and frozen DLBCL tissues. To study the functional roles of the downregulated hsa-miR-28-5p in DLBCL, a Cell Counting Kit-8 assay was conducted to estimate cell proliferation. Transient transfection of miRNA mimics was performed to overexpress hsa-miR-28-5p, and flow cytometry was performed to examine cell apoptosis and cell cycle progression. A dual-luciferase reporter assay was employed to explore the relationship between hsa-miR-28-5p and YWHAZ. Western blotting and qRT-PCR were used to investigate the function of hsa-miR-28-5p in YWHAZ expression. hsa-miR-28-5p was found to be significantly downregulated in DLBCL tissues and cell lines. Functional studies showed that hsa-miR-28-5p overexpression inhibited cell viability and proliferation, and YWHAZ was predicted to be a target of hsa-miR-28-5p. Dual-luciferase reporter assay, Western blotting, and qRT-PCR verified that hsa-miR-28-5p negatively regulated YWHAZ expression by directly targeting its 3' untranslated regions in DLBCL cells. hsa-miR-28-5p may suppress the growth of DLBCL cells by inhibiting YWHAZ expression. These findings could provide novel targets for DLBCL diagnosis and therapy.