MicroRNA-766-3p Inhibits Tumour Progression by Targeting Wnt3a in Hepatocellular Carcinoma

Yu You,Keting Que,Yun Zhou,Zhen Zhang,Xiaoping Zhao,Jianpin Gong,Zuojin Liu 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.9

Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR-766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear β-catenin level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 upregulation increased the nuclear β-catenin level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the β-catenin-TCF4 interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.

Transcriptional regulation of Glis2 in hepatic fibrosis

Gong Huan-Yu,Zhou Peng-Cheng,Zhang Hao-Ye,Chen Li-Min,Zhou Yang-Mei,Liu Zhen-Guo 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

The role of Gli-similar 2 (Glis2) in hepatic fibrosis (HF) is controversial. In this study, we focused on the functional and molecular mechanisms involved in the Glis2-mediated activation of hepatic stellate cells (HSCs)—a milestone event leading to HF. The expression levels of Glis2 mRNA and protein were significantly decreased in the liver tissues of patients with severe HF and in mouse fibrotic liver tissues as well as HSCs activated by TGFβ1. Functional studies indicated that upregulated Glis2 significantly inhibited HSC activation and alleviated BDL-induced HF in mice. Downregulation of Glis2 was found to correlate significantly with DNA methylation of the Glis2 promoter mediated by methyltransferase 1 (DNMT1), which restricted the binding of hepatic nuclear factor 1-α (HNF1-α), a liver-specific transcription factor, to Glis2 promoters. In addition, the enrichment of DNMT1 in the Glis2 promoter region was mediated by metastasis-associated lung adenocarcinoma transcriptor-1 (MALAT1) lncRNA, leading to transcriptional silencing of Glis2 and activation of HSCs. In conclusion, our findings reveal that the upregulation of Glis2 can maintain the resting state of HSCs. The decreased expression of Glis2 under pathological conditions may lead to the occurrence and development of HF with the expression silencing of DNA methylation mediated by MALAT1 and DNMT1.

New Method to Improve the Secondary Path Modeling Accuracy for Active Noise Control Systems

Shan-zhen Yi,Ren-yuan Fei,Da-sen Zhou,Tai-wen Liu,Jian-ping Yu,Jin-feng Yang,Kui-cheng Gong 한국소음진동공학회 2003 한국소음진동공학회 국제학술대회논문집 Vol.2003 No.8

MicroRNA-766-3p Inhibits Tumour Progression by Targeting Wnt3a in Hepatocellular Carcinoma

You, Yu,Que, Keting,Zhou, Yun,Zhang, Zhen,Zhao, Xiaoping,Gong, Jianpin,Liu, Zuojin Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.9

Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear ${\beta}-catenin$ level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 upregulation increased the nuclear ${\beta}-catenin$ level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the ${\beta}-catenin-TCF4$ interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry

Zhou, Lei,Yu, Lan,Feng, Zhen-Zhong,Gong, Xiao-Meng,Cheng, Ze-Nong,Yao, Nan,Wang, Dan-Na,Wu, Shi-Wu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Background: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. Materials and Methods: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. Results: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was $21.7{\pm}11.1$ in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (${\geq}22$) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). Conclusions: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.

Nitrogen, phosphorus and potassium fertilization promotes Zanthoxylum armatum ‘Hanyuan Putao Qingjiao’ fl ower bud diff erentiation in Sichuan, China

Chaobin Zhou,Yu Cai,Zhen’an Yang,Hongmin Wang,Fang Deng,Zeping Bai,Wei Gong,Jingyan Wang 한국원예학회 2020 Horticulture, Environment, and Biotechnology Vol.61 No.4

Chinese prickly ash is an ecologically and economically important tree species. In southwestern China, its yield is low dueto severe fruit and fl ower drop related to the relatively low nutrient status of shoots and/or fl owers caused by a lack of nutrientsupply. Therefore, studies on fl ower bud diff erentiation are of great importance to improve the yield of Chinese pricklyash. An orthogonal experimental design was used to study the eff ects of N (urea, 97.8, 195.7 and 391.3 g/individual), P(superphosphate, 150, 300 and 600 g/individual) and K (potassium sulphate, 83.3, 166.7 and 333.3 g/individual) treatmentson fl ower bud diff erentiation in 3-year-old Zanthoxylum armatum ‘Hanyuan Putao Qingjiao’ trees. The results showed thatN, P and K fertilizer application signifi cantly increased the fl ower bud diff erentiation rate, branch diameter and number, thesoluble sugar content, the soluble protein content, the C/N ratio, the ABA content and the ABA/IAA ratio but decreasedthe GA content and IAA content in Chinese prickly ash. The fl ower bud diff erentiation rate was positively related to thesoluble sugar content, soluble protein content, C/N ratio and ABA/IAA ratio ( p < 0.05) but negatively related to GA andIAA ( p < 0.05). A higher P content increased the accumulation of nutrients and ABA in the buds, thereby promoting thefl ower bud diff erentiation in Z. armatum ‘Hanyuan Putao Qingjiao’. From these results, the fl ower bud diff erentiation in Z. armatum ‘Hanyuan Putao Qingjiao’ requires appropriate N, P and K fertilizer ratios and amounts. Treatment 12 (N 2 P 3 K 1 )signifi cantly improved the absorption of nutrients in the buds and promoted the diff erentiation of fl ower buds.

BMB Reports : Heat shock protein 90β inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt

( Shuai Zhang ),( Yong Sun ),( Zhi Qiang Yuan ),( Ying Li ),( Xiao Lu Li ),( Zhen Yu Gong ),( Yi Zhi Peng ) 생화학분자생물학회(구 한국생화학분자생물학회) 2013 BMB Reports Vol.46 No.1

Intestinal epithelial cell (IEC) apoptosis induced by hypoxia compromise intestinal epithelium barrier function. Both Akt and Hsp90 have cytoprotective function. However, the specific role of Akt and Hsp90β in IEC apoptosis induced by hypoxia has not been explored. We confirmed that hypoxia-induced apoptosis was reduced by Hsp90β overexpression but enhanced by decreasing Hsp90β expression. Hsp90β overexpression enhanced BAD phosphorylation and thus reduced mitochondrial release of cytochrome C. Reducing Hsp90β expression had opposite effects. The protective effect of Hsp90β against apoptosis was negated by LY294002, an Akt inhibitor. Further study showed that Akt phosphorylation was enhanced by Hsp90β, which was not due to the activation of upstream PI3K and PDK1 but because of stabilization of pAkt via direct interaction between Hsp90β and pAkt. These results demonstrate that Hsp90β may play a significant role in protecting IECs from hypoxia-induced apoptosis via stabilizing pAkt to phosphorylate BAD and reduce cytochrome C release. [BMB Reports 2013; 46(1): 47-52]