Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway

Abstract

Background The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. Methods MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. Results MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. Conclusion These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC.

E2F6/KDM5C promotes SF3A3 expression and bladder cancer progression through a specific hypomethylated DNA promoter

“…All BC patients underwent curative radical cystectomy in urology department. The research protocol and sample collection were approved by the Ethics Committee of the Second Hospital of Hebei Medical University, and each patient signed a written informed consent [ 26 ].…”

“…Sanger sequencing was used to confirm the sequence. BC cell lines were seeded into a 24-well plate, and SF3A3-prom vector, oeKDM5C, or shE2F6 and the corresponding control vector were co-transfected to cells for 24 h. Luciferase activity was measured by Dual-Glo Luciferase Assay System (Promega, Madison, WI, USA) with Flash and Glow (LB955, Berthold Technologies) [ 26 ].…”

Roles of Myc‐associated zinc finger protein in malignant tumors

“…Research by Ren LX et al 64 . showed that MAZ was highly expressed in clear cell renal carcinoma (ccRCC) tissues, and upregulation of MAZ promoted the proliferation of ccRCC cells in vitro.…”

Disturbing NLRP3 acetylation and inflammasome assembly inhibits androgen receptor‐promoted inflammatory responses and prostate cancer progression

“…Immunofluorescence staining was performed as described previously. 19,21 Briefly, paraffin tissue sections were deparaffinized with xylene and rehydrated with gradient ethanol. The sections were immersed in PBS containing 0.5% Triton X-100 for 20 min and then washed thrice with PBS for 5 min each time.…”

“…Paraffin-embedded sections (4-μm thick) of clinical tissues were deparaffinized and subjected to in situ hybridization, as described previously. 19,21 According to the miRCURY LNATM microRNA ISH optimization kit manual (Exiqon, Vedbaek, Denmark), hybridization was performed with a fluorescent-labeled circAR-3 probe in hybridization buffer at 55°C for 1 h. The samples were washed in SSC buffer and sealed using DAPI Fluoromount-G. The images were captured using confocal microscopy (DM6000 CFS, Leica) and processed with LAS AF software.…”