Pokemon enhances proliferation, cell cycle progression and anti-apoptosis activity of colorectal cancer independently of p14ARF–MDM2–p53 pathway

Abstract

Pokemon has been showed to directly suppress p14(ARF) expression and also to overexpress in multiple cancers. However, p14(ARF)-MDM2-p53 pathway is usually aberrant in colorectal cancer (CRC). The aim is to confirm whether Pokemon plays a role in CRC and explore whether Pokemon works through p14(ARF)-MDM2-p53 pathway in CRC. Immunohistochemistry for Pokemon, p14(ARF) and Mtp53 protein was applied to 45 colorectal epitheliums (CREs), 42 colorectal adenomas (CRAs) and 66 CRCs. Pokemon was knocked down with RNAi technique in CRC cell line Lovo to detect mRNA expression of p14(ARF) with qRT-PCR, cell proliferation with CCK8 assay, and cell cycle and apoptosis with flowcytometry analysis. The protein expression rates were significantly higher in CRC (75.8%) than in CRE (22.2 %) or CRA (38.1%) for Pokemon and higher in CRC (53.0%) than in CRE (0) or CRA (4.8%) for Mtp53, but not significantly different in CRC (86.4 %) versus CRE (93.3%) or CRA (90.5 %) for p14(ARF). Higher expression rate of Pokemon was associated with lymph node metastasis and higher Duke's stage. After knockdown of Pokemon in Lovo cells, the mRNA level of p14(ARF) was not significantly changed, the cell proliferation ability was decreased by 20.6%, cell cycle was arrested by 55.7% in G0/G1 phase, and apoptosis rate was increased by 19.0%. Pokemon enhanced the oncogenesis of CRC by promoting proliferation, cell cycle progression and anti-apoptosis activity of CRC cells independently of p14(ARF)-MDM2-p53 pathway. This finding provided a novel idea for understanding and further studying the molecular mechanism of Pokemon on carcinogenesis of CRC.

A Zbtb7a proto‐oncogene as a novel target for miR‐125a

“…In addition, WT1 was shown to promote cell cycle progression from G1‐ to S‐phase in lung and breast cancer cells . Zbtb7a was also reported to inhibit apoptosis and promote cell cycle progression from G1‐ to S‐phase in colon and cervical cancer cells through suppression of apoptosis and cell cycle regulators, p21 and p53 . The present study demonstrated that knockdown of Zbtb7a expression resulted in apoptosis and G1‐phase cell cycle arrest in lung cancer cells.…”

“…The present study for the first time identified Zbtb7a (also known as FBI‐1, LRF, and Pokemon), which was characterized as a potential proto‐oncogene in cellular transformation , as a novel direct target for miR‐125a. It has been reported that Zbtb7a is overexpressed in lymphoma and various types of solid tumors including lung , breast , and colon cancers , and that high expression levels of Zbtb7a are correlated with proliferation (high Ki‐67 positivity), tumor size, and poor prognosis in lung cancer . These findings suggest that Zbtb7a is involved in the development and progression of various kinds of cancers.…”

Negative feedback loop between ZBTB7A and TGF-β in breast cancer

“…These results suggest an important function for ZBTB7A in carcinogenesis. ZBTB7A is considered to be an oncogenic transcription factor in multiple types of cancer, including in colorectal and oral cancer (27,28). However, previous studies have revealed that ZBTB7A may also act as a tumor suppressor through the transcriptional repression of glycolysis in colon cancer (29), suppression of melanoma cell adhesion molecule in melanoma (7), and inhibition of a SRY-box 9-dependent pathway for tumor invasion and the bypassing of cellular senescence in prostate cancer (6).…”

Y Box-Binding Protein 1 Promotes Epithelial-Mesenchymal Transition, Invasion, and Metastasis of Cervical Cancer via Enhancing the Expressions of Snail

“…20 The SP-9000 immunohistochemistry kit including the secondary antibodies and ABC was obtained from Zhongshan Jinqiao Biological Technology Co, Ltd, Beijing, China. The primary antibodies were antiYhuman YB-1 polyclonal antibody (1:5000, rabbit, Cat: ab12148, Abcam), antiYhuman Snail polyclonal antibody (1:100, rabbit, Cat: NBP1-19529, Novus), and antiYhuman E-cad monoclonal antibody (1:1000, mouse, Cat: ab1416, Abcam).…”