Upregulated PPARG2 facilitates interaction with demethylated AKAP12 gene promoter and suppresses proliferation in prostate cancer

Abstract

Prostate cancer (PCA) is one of the most common male genitourinary tumors. However, the molecular mechanisms involved in the occurrence and progression of PCA have not been fully clarified. The present study aimed to investigate the biological function and molecular mechanism of the nuclear receptor peroxisome proliferator-activated receptor gamma 2 (PPARG2) in PCA. Our results revealed that PPARG2 was downregulated in PCA, and overexpression of PPARG2 inhibited cell migration, colony formation, invasion and induced cell cycle arrest of PCA cells in vitro. In addition, PPARG2 overexpression modulated the activation of the Akt signaling pathway, as well as inhibited tumor growth in vivo. Moreover, mechanistic analysis revealed that PPARG2 overexpression induced increased expression level of miR-200b-3p, which targeted 3′ UTR of the downstream targets DNMT3A/3B, and facilitated interaction with demethylated AKAP12 gene promoter and suppressed cell proliferation in PCA. Our findings provided the first evidence for a novel PPARG2-AKAP12 axis mediated epigenetic regulatory network. The study identified a molecular mechanism involving an epigenetic modification that could be possibly targeted as an antitumoral strategy against prostate cancer.

AKAP12 ameliorates liver injury via targeting PI3K/AKT/PCSK6 pathway

“…6 E). Previous studies demonstrated that knockout or silencing of AKAP12 activates the PI3K/AKT pathway [ 32 , 33 ]. Therefore, cell lines were constructed with AKAP12 overexpression plasmids, which revealed that AKAP12 overexpression inhibited the PI3K/AKT pathway ( Fig.…”

The Cardiac Glycoside Deslanoside Exerts Anticancer Activity in Prostate Cancer Cells by Modulating Multiple Signaling Pathways

“…A colony formation assay was conducted as previously described [ 20 ]. Briefly, PCa cells were seeded onto 6-well plates at 1000 cells per well, treated with deslanoside at 0, 60, and 120 nM for 13 days for 22Rv1 cells and 0, 40, and 80 nM for 10 days for PC-3 and DU 145 cells.…”

Regulatory functions of miR‑200b‑3p in tumor development (Review)

“…miR-200b-3p can exert different functions depending on the type of tumor. For instance, in most cases, it exhibits tumor-suppressive effects and is therefore downregulated, with examples of such tumors being colorectal cancer (CRC) (4-7), hepatocellular carcinoma (HCC) (8)(9)(10)(11)(12), pancreatic cancer (13,14), gastrointestinal stromal tumors (15), breast cancer (16)(17)(18), melanoma (19), glioblastoma (20), glioma (21), thyroid carcinoma (22), cemento-ossifying fibroma (23), esophageal cancer (24,25), oral squamous cell carcinoma (26), prostate cancer (27,28), renal cell carcinoma (29), bladder cancer (30), and malignant mesothelioma (31). However, as already noted, this microRNA can also be oncogenic in various types of cancers, with examples of such tumors being prostate cancer (32,33), lung cancer (34)(35)(36)(37)(38), oral squamous cell carcinoma (39), esophageal squamous cell carcinoma (40), breast cancer (41), colorectal cancer (42,43), neck cancer (44), cholangiocarcinoma (45), and hepatocellular carcinoma (46).…”

“…The former, as an oncogene (53), is not only involved in adipogenesis but is also significantly upregulated in metastatic lesions compared with primary tumors in prostate cancer (53). In contrast, the protein products of DNMT3A/3B are both enzymes that act on DNA sequences to catalyze the methylation of CpG and by targeting DNMT3A/3B, miR-200b-3p facilitates interactions between peroxisome proliferator-activated receptor γ 2 (PPARG2) and demethylated A-kinase anchoring protein 12 (AKAP12) gene promoter to suppress the growth of prostate cancer (27). However, Janiak et al found that, in prostate cancer, miR-200b-3p could even regulate the level of tissue inhibitor of metalloproteinase 4 (TIMP4) expression (33), with this regulation being mediated by ZEB1 and ETS proto-oncogene 1 (ETS1) which represent two targets of miR-200b-3p (33).…”