Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma

Abstract

In Myanmar, hepatocellular carcinoma (HCC) is commonly seen in young adult and associated with poor prognosis, while the molecular mechanisms that characterize HCC in Myanmar are unknown. As co-activation of Wnt/β-catenin signaling and c-Myc (Myc) are reported to associate with malignancy of HCC, we immunohistochemically investigated the expression of Pygo2 and Bcl9, the co-activators of the Wnt/β-catenin signaling, Myc and PCNA in 60 cases of Myanmar HCC. Pygo2 expression was confirmed by in situ hybridization. The signal intensity was measured by image analyzer and then statistically analyzed. As a result, the expression of Pygo2 was significantly higher in HCC compared to normal liver tissue and the nuclear signal was the most intense in poorly differentiated HCC. Cytoplasmic Bcl9 was expressed in the normal liver tissue but decreased in HCC with the progression of histopathological grade. Myc was significantly higher in poorly differentiated HCC, whereas PCNA labeling index increased with the progression of histopathological grade. Nuclear Pygo2 showed strong correlation with nuclear Myc (P < 0.01) and PCNA (P < 0.001), and inversely correlated with cytoplasmic Bcl9 (P < 0.01). Our results suggested Wnt/β-catenin and Myc signaling is commonly activated in Myanmar HCC and that the correlative upregulation of nuclear Pygo2 and Myc characterizes the malignant features of HCC in Myanmar.

Interference of EFNA4 suppresses cell proliferation, invasion and angiogenesis in hepatocellular carcinoma by downregulating PYGO2

“…Meanwhile, downregulation of PYGO2 could inhibit HCC cell invasion in vitro and metastasis in xenograft tumor models, highlighting that targeting PYGO2 potentially inhibited metastasis of HCC. 13 , 20 , 21 In the present study, a potential interaction between EFNA4 and PYGO2 was predicted by Humanbase ( https://hb.flatironinstitute.org/ ), which was further verified using Co-IP assay. In addition, EFNA4 could positively regulate PYGO2 expression, and the results from following rescued experiments showed that simultaneous EFNA4 knockdown and PYGO2 overexpression recovered the phenotypes defect resulted from EFNA4 knockdown, suggesting that EFNA4 might exert its function in Huh7 cells partly by targeting PYGO2.…”

Histopathological evaluation of PYGO2 expression in esophageal squamous cell carcinoma

“…[18]. In hepatocellular carcinoma (HCC), Wnt/β-catenin and Myc signaling is upregulated that the correlative overexpression of nuclear PYGO2 and Myc represent the malignant characteristics of HCC [19]. In addition to the in vivo and in vitro functional assays, the clinical expression analysis discovered that high PYGO2 expression acts as an oncogenic driver of prostate cancer, which overexpression of PYGO2 protein was related to LNM and bone metastasis, high-grade cancer, and biochemical recurrence (BCR) [20].…”

Transcriptome Profiling of Anhidrotic Eccrine Sweat Glands Reveals that Olfactory Receptors on Eccrine Sweat Glands Regulate Perspiration in a Ligand-Dependent Manner

“…In situ hybridization was performed as described previously ( Htun et al., 2021 , Koji and Brenner, 1993 ). Briefly, sections were deparaffinized, rehydrated, treated with 0.2 N hydrogen chloride for 20 minutes, and then treated with 50 μg/ml proteinase K (Wako, Osaka, Japan) at 37 °C for 15 minutes.…”