REGγ is a strong candidate for the regulation of cell cycle, proliferation and the invasion by poorly differentiated thyroid carcinoma cells

Abstract

REGγ is a proteasome activator that facilitates the degradation of small peptides. Abnormally high expression of REGγ has been observed in thyroid carcinomas. The purpose of the present study was to explore the role of REGγ in poorly differentiated thyroid carcinoma (PDTC). For this purpose, small interfering RNA (siRNA) was introduced to down-regulate the level of REGγ in the PDTC cell line SW579. Down-regulation of REGγ at the mRNA and protein levels was confirmed by RT-PCR and Western blot analyses. FACS analysis revealed cell cycle arrest at the G1/S transition, the MTT assay showed inhibition of cell proliferation, and the Transwell assay showed restricted cell invasion. Furthermore, the expression of the p21 protein was increased, the expression of proliferating cell nuclear antigen (PCNA) protein decreased, and the expression of the p27 protein was unchanged as shown by Western blot analyses. REGγ plays a critical role in the cell cycle, proliferation and invasion of SW579 cells. The alteration of p21 and PCNA proteins related to the down-regulation of REGγ suggests that p21 and PCNA participate in the process of REGγ regulation of cell cycle progression and cell proliferation. Thus, targeting REGγ has a therapeutic potential in the management of PDTC patients.

REGγ regulates ERα degradation via ubiquitin–proteasome pathway in breast cancer

“…REGc is highly expressed in many cancers including the breast cancer [6][7][8][9][10]. One possibility is that the high expression of REGc is a bi-product and has little effect on cancer growth.…”

“…It can stimulate the proteolytic activity of 20S proteasome and enable protein/peptide substrates to diffuse into the environment of proteasomes [4,5]. REGc has been reported to be highly expressed in human breast cancers [6,7], thyroid cancers [8], hepatocellular carcinomas [9] and colorectal cancers [10]. In addition, recent studies have showed that REGc play a role in protein degradation of tumor suppressor p53 [11,12], oncogene steroid receptor coactivator-3 (SRC-3) [13], as well as cell cycle regulator proteins including p21, p16 and p19 [14].…”

Expression of Proteasome Activator REGγ in Human Laryngeal Carcinoma and Associations with Tumor Suppressor Proteins

“…Moreover, the expression of REGγ has been found abnormally high in human breast cancer cells and the metastatic lymph nodes (Wang et al, 2009). Recently, there has study showed that REGγ was a strong candidate for the regulation of cell cycle, proliferation and the invasion in poorly differentiated thyroid carcinoma cells (Zhang et al, 2012). Despite these interesting observations, the pathological contributions of the REGγ to the development of cancer remain unclear.…”

Knockdown of REGγ inhibits the proliferation and migration and promotes the apoptosis of multiple myeloma cells by downregulating NF-κB signal pathway

“…REGγ, also known as proteasome activator subunit 3, is an ATP-and ubiquitin-independent proteasome activator [6]. It is evident that REGγ is involved in the progression of cancers [7,8].…”