Knockdown of RNF2 induces cell cycle arrest and apoptosis in prostate cancer cells through the upregulation of TXNIP

Abstract

RNF2, also known as RING1b or RING2, is identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), which mediates the mono-ubiquitination of histone H2A. RNF2 has been proved to have oncogenic function in many kinds of cancers, but the function of RNF2 in prostate cancer (PCa) has not been evaluated. Here we show that PCa tissues showed higher RNF2 expression than the benign prostatic hyperplasia (BPH) tissues. Knockdown of RNF2 in PCa cells resulted in cell cycle arrest, increased apoptosis and inhibited cell proliferation, and the growth of RNF2 knockdown PCa xenografts were obviously inhibited in nude mice. Gene microarray analysis was performed and tumor suppressor gene TXNIP was found to be significantly increased in RNF2 knockdown cells. Simultaneously knockdown of RNF2 and TXNIP can partially rescue the arrested cell cycle, increased apoptosis and inhibited cell proliferation in RNF2 single knockdown cells. Furthermore, ChIP assay result showed that RNF2 enriched at the TXNIP promoter, and the enrichment of RNF2 and ubiquitination of H2A in TXNIP promoter was obviously inhibited in RNF2 knockdown cells. In conclusion, our results demonstrate that RNF2 functions as an oncogene in PCa and RNF2 may regulate the progression of PCa through the inhibition of TXNIP.

MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

“…When tumor was grown at about 3 months, the tumor was taken out and measured in vitro for the comparison of tumor size. Tumor volume was calculated as length × width 2 /2, where the length and width are the longest and shortest axes in millimeters [23]. …”

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

“…Further ES cell studies revealed that RNF2 target genes repress Wnt signaling [223]. One of the latest in vitro studies showed that knockdown of Rnf2 promotes cell-cycle arrest and apoptosis in prostate cancer cells [233] and gastric cancer cells [234].…”

Thioredoxin‐interacting protein induced α‐synuclein accumulation via inhibition of autophagic flux: Implications for Parkinson's disease

“…Thioredoxin‐interacting protein (TXNIP) is the endogenous inhibitor of reactive oxygen species (ROS) elimination, by binding to the active cysteine residue of thioredoxin, resulting in oxidative stress . TXNIP overexpression renders cells more susceptible to oxidative stress and promotes apoptosis . It was reported that downregulation of TXNIP prevented retinal neurodegeneration .…”

“…11 TXNIP overexpression renders cells more susceptible to oxidative stress and promotes apoptosis. 12 It was reported that downregulation of TXNIP prevented retinal neurodegeneration. 13 However, research reporting the role of TXNIP in PD is rare.…”