Review
Biochemistry & Molecular Biology
Eun Jin Sun, Miriam Wankell, Pranavan Palamuthusingam, Craig McFarlane, Lionel Hebbard
Summary: This review article discusses the pivotal role of the PI3K/Akt/mTOR pathway in HCC, focusing on its impact on cellular processes and providing an update on the ongoing clinical development of therapies targeting this pathway for HCC treatments.
Review
Pharmacology & Pharmacy
Jieun Bang, Mihyeon Jun, Soyun Lee, Hyuk Moon, Simon Weonsang Ro
Summary: Hepatocellular carcinoma (HCC) is a significant global health concern, with its incidence steadily increasing. Recent progress has been made in understanding the molecular signaling pathways, particularly the EGFR/PI3K/AKT/mTOR pathway, which plays a central role in HCC. Preclinical studies have shown the effectiveness of targeting this signaling pathway for HCC therapy, offering potential therapeutic options for patients.
Article
Pharmacology & Pharmacy
Xiang-Peng Tan, Ben-Han Xiong, Yuan-Xu Zhang, Shen-Li Wang, Qian Zuo, Jing Li
Summary: This study discovered the highly expressed FXYD5 in sorafenib-resistant HCC cells and its higher expression level in HCC tissues compared to par-acancerous tissues. The downregulation of FXYD5 reversed the resistance of Huh7/sora cells to sorafenib, while overexpression of FXYD5 reduced the sensitivity of HCC cells to sorafenib. Additionally, abnormal activation of the Akt/mTOR signaling pathway was found in Huh7/sora cells, and MK2206, an Akt inhibitor, increased the sensitivity of HCC cells to sorafenib. The expression level of p-Akt was positively correlated with the expression of FXYD5 in HCC tissues.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Oncology
Yao Zhang, Xiaopei Hao, Guoyong Han, Yiwei Lu, Zhiqiang Chen, Long Zhang, Jindao Wu, Xuehao Wang
Summary: This study systematically investigated the expression and clinical significance of GINS2 in HCC, and revealed its important role in the progression of HCC through functional enrichment analysis and experimental validation. The results suggest that GINS2 may serve as a crucial diagnostic and therapeutic target for HCC.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Medicine, Research & Experimental
Yanqing Ye, Maosheng Liu, Fengfei Wu, Shiyu Ou, Weidong Wang, Jieying Fei, Fang Xie, Lan Bai
Summary: TRMT6 is overexpressed in HCC tissues and associated with TNM stage, T classification, and N classification. Overexpression of TRMT6 promotes HCC cell proliferation through the PI3K/AKT/mTOR axis in vivo and in vitro. Inhibition of TRMT6 reduces tumor growth and is related to the PI3K/AKT pathway.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Zhangya Pu, Dan G. Duda, Yuanyuan Zhu, Siya Pei, Xiaofang Wang, Yan Huang, Panpan Yi, Zebing Huang, Fang Peng, Xingwang Hu, Xuegong Fan
Summary: This study found that VCP is significantly increased in HCC tissues and is associated with advanced TNM stages and poorer prognosis. VCP overexpression promotes HCC cell proliferation, migration, and invasion via PI3K/AKT/mTOR pathway activation. Additionally, VCP interacts with HMGB1 and enhances its protein stability, contributing to HCC progression.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, General & Internal
Peng Du, Kaifeng Luo, Guoyong Li, Jisheng Zhu, Qi Xiao, Yong Li, Xingjian Zhang
Summary: The study revealed that PRMT4 is highly expressed in HCC and closely associated with clinical characteristics and prognosis of liver cancer. PRMT4 promotes proliferation, migration, and invasion of HCC cells by activating the AKT/mTOR signaling pathway.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Oncology
Shimin Lu, Yinghui Liu, Shan Tian, Yang He, Weiguo Dong
Summary: This study found that KIFC3 is upregulated in hepatocellular carcinoma (HCC) and high expression is associated with poor overall survival. Further experiments showed that inhibition of KIFC3 can suppress proliferation, migration, and invasion of HCC cells, as well as impede HCC growth. Mechanistically, KIFC3 promotes HCC progression through the PI3K/AKT/mTOR signaling pathway.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Chemistry, Medicinal
Linlin Wang, Li Cheng, Li Ma, Ammad Ahmad Farooqi, Gan Qiao, Yuxi Zhang, Hanlin Ye, Minghua Liu, Jianlin Huang, Xiaohui Yang, Xiukun Lin, Shousong Cao
Summary: Alnustone exhibits potent growth inhibition against hepatocellular carcinoma (HCC) by inducing apoptosis and inhibiting the PI3K/Akt/mTOR/p70S6K pathway.
PHYTOTHERAPY RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Jing Man, Wanbiao Zhou, Shi Zuo, Xueke Zhao, Qiang Wang, Huaxing Ma, Hai-Yang Li
Summary: TANGO1 promotes hepatocellular carcinoma by activating the PI3K/AKT/mTOR signaling pathway through interaction with NRTN, leading to increased proliferation and EMT. The TANGO1/NRTN axis may serve as a potential therapeutic target for HCC.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Eslam E. Abd El-Fattah, Sameh Saber, Mahmoud E. Youssef, Hanan Eissa, Eman El-Ahwany, Noha A. Amin, Mohammed Alqarni, Gaber El-Saber Batiha, Ahmad J. Obaidullah, Mohamed M. Y. Kaddah, Ahmed Gaafar Ahmed Gaafar, Ahmed A. E. Mourad, Gomaa Mostafa-Hedeab, Amir Mohamed Abdelhamid
Summary: This study demonstrates that sitagliptin inhibits the activation of HIF-1α by interfering with the AKT-AMPKα-mTOR axis and interrupting IKKβ, P38α, and ERK1/2 signals. Sitagliptin prolongs survival, improves liver function, inhibits angiogenesis and tissue invasion, promotes apoptosis, inhibits proliferation, reduces inflammation, and has antifibrotic potential.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Surgery
Sunbin Ling, Qifan Zhan, Guangjiang Jiang, Qiaonan Shan, Lu Yin, Rui Wang, Qingyang Que, Xuyong Wei, Shengjun Xu, Jiongjie Yu, Wei Zhou, Lincheng Zhang, Jiaqi Bao, Qianwei Ye, Renyi Su, Rongli Wei, Jimin Liu, Kangchen Chen, Jingrui Wang, Haiyang Xie, Shusen Zheng, Xin He, Jiajia Xiang, Xiao Xu
Summary: This study discovered that E2F7 gene induces and promotes resistance to mTOR inhibitor sirolimus in HCC under hypoxic conditions. This is achieved by suppressing mTOR complex 1 and activating hypoxia-inducible factor-1 alpha and its downstream genes. Low expression of E2F7 can serve as an effective biomarker for predicting the response to anti-mTOR-based therapies after LT in HCC patients. Targeting E2F7 synergistically inhibits HCC growth with sirolimus.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Environmental Sciences
Jiawei Hong, Xiaoyan Wang, Hangbiao Jin, Yuanchen Chen, Yifan Jiang, Keyi Du, Diyu Chen, Shusen Zheng, Linping Cao
Summary: This study reveals that PFOA can promote the growth of hepatocellular carcinoma and activates specific signaling pathways. The presence of PFOA is a serious environmental pollution issue that poses a threat to human health and ecological integrity.
ENVIRONMENTAL POLLUTION
(2024)
Article
Chemistry, Medicinal
Nari Shin, Hyo-Jung Lee, Deok Yong Sim, Eunji Im, Ji Eon Park, Woon Yi Park, Ah Reum Cho, Bum Sang Shim, Sung-Hoon Kim
Summary: This study investigated the mechanism of action of Compound K, an active ginseng saponin metabolite, in human hepatocellular carcinoma cells, revealing that it induces apoptosis through inhibition of glycolysis and AKT/mTOR/c-Myc signaling. These findings suggest that Compound K could be a promising candidate for liver cancer therapy.
PHYTOTHERAPY RESEARCH
(2021)
Article
Cell Biology
Guoliang Shen, Hao Wang, Ning Zhu, Qiliang Lu, Junwei Liu, Qiuran Xu, Dongsheng Huang
Summary: Hypoxia, a critical characteristic of hepatocellular carcinoma, contributes to the progression and resistance of the disease. In this study, the researchers identified RNF146 as a novel target gene regulated by HIFs. RNF146 overexpression was found in HCC tissues and cell lines, and was associated with poor prognosis. Further analysis revealed that RNF146 promotes HCC progression through the activation of the AKT/mTOR pathway by regulating PTEN protein levels.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jie Zhang, Qianqian Song, Mengna Wu, Wenjie Zheng
Summary: Exosomes play crucial roles in chemoresistance of HCC cells by regulating various biological processes that promote drug resistance, making them a potential target to reverse chemoresistance and a candidate biomarker of drug efficacy in HCC patients.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Mengqi Zhu, Yuting Huang, Saiyan Bian, Qianqian Song, Jie Zhang, Wenjie Zheng, Chun Cheng
Summary: Understanding organogenesis, disorders, and repairing processes is crucial for disease treatment and prevention. Organoids, a 3D culture system in vitro, are becoming increasingly important in liver research for establishing disease models and conducting in-depth studies.
CURRENT MOLECULAR PHARMACOLOGY
(2021)
Article
Cell Biology
Wenkai Ni, Shengli Lin, Saiyan Bian, Mingbing Xiao, Yongjun Wang, Yumin Yang, Cuihua Lu, Wenjie Zheng, Pinghong Zhou
Summary: A novel porous composite scaffold, ChCo-TAMS, composed of chitosan, collagen-I and triamcinolone acetonide loaded into poly (lactic-co-glycolic) acid microspheres, displayed unique properties in inhibiting the activation of macrophages, chemokine-mediated cell recruitment and fibrogenesis of fibroblasts, providing a promising clinical medical device for the prevention of post-operative oesophageal stricture.
CELL PROLIFERATION
(2021)
Article
Biochemistry & Molecular Biology
Wenjie Zheng, Jie Zhang, Qianqian Song, Yuqing Xu, Mengqi Zhu, Jianguo Ma
Summary: Bladder cancer remains a challenging malignancy with unclear molecular pathogenesis. The study identified RAC3 as a key gene associated with poor prognosis in bladder cancer patients, suggesting its potential as a novel prognostic biomarker. Further investigation is warranted to explore the role of RAC3 in bladder cancer progression and its correlation with malignant phenotypes and immune infiltration.
DNA AND CELL BIOLOGY
(2021)
Article
Oncology
Wenkai Ni, Saiyan Bian, Mengqi Zhu, Qianqian Song, Jianping Zhang, Mingbing Xiao, Wenjie Zheng
Summary: The study systematically investigated the expression features and clinical significance of USPs in hepatocellular carcinoma (HCC). Overexpression of USPs was correlated with aggressive characteristics and poor prognosis in HCC tissues. A risk signature formed by eight USPs showed robust prognostic significance and could predict overall survival of HCC patients in different cohorts. The study highlights the targeted value of USPs for HCC treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Saiyan Bian, Wenkai Ni, Mengqi Zhu, Xue Zhang, Yuwei Qiang, Jianping Zhang, Zhiyu Ni, Yiping Shen, Shi Qiu, Qianqian Song, Mingbing Xiao, Wenjie Zheng
Summary: In this study, it was found that overexpression of FEN1 in hepatocellular carcinoma (HCC) is associated with poor prognosis. FEN1 inactivates the P53 signaling pathway by preventing the degradation of MDM2 and promotes malignant phenotypes in HCC cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Chemistry, Physical
Jie Ji, Dandan Jin, Minxue Xu, Yujie Jiao, Yue Wu, Tong Wu, Renjie Lin, Wenjie Zheng, Zhaoxiu Liu, Feng Jiang, Yihui Fan, Mingbing Xiao
Summary: This study identified AKR1B1 as an upregulated gene in pancreatic cancer, which promotes exosome secretion and cell migration. AKR1B1 negatively regulates lysosomal function and multivesicular body (MVB) degradation. The findings highlight the critical role of AKR1B1 in pancreatic cancer and suggest that pharmacological targeting of AKR1B1 may be an effective strategy to inhibit tumor growth and metastasis.
Article
Oncology
Yijian Zhang, Li Li, Wenjie Zheng, Lei Zhang, Ninghua Yao
Summary: This study explores the clinical significance of the tumor immune microenvironment in HNSCC. It found that infiltration of CD8(+) T cells is associated with prognosis, and developed a clinical classifier based on CD8(+) T cells to predict the prognosis of HNSCC patients.
ANNALS OF TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Yuwei Qiang, Ninghua Yao, Fan Zuo, Shi Qiu, Xiaolei Cao, Wenjie Zheng
Summary: Cancer is a major cause of death and a significant global public health threat. Organoid, a novel 3D in vitro model, has been utilized in various tumor-related studies due to its advantages. The construction methods of organoids include Matrigel-dependent 3D culture system, Air-Liquid Interface (ALI) culture, and Microfluidic culture or Organ-on-chips platform. In cancer studies, organoid models can effectively depict key features, identify potential targets, investigate driver genes, and explore risk or protective factors. Moreover, organoid systems have been used to discover preventive drugs for tumors. The current evidence highlights the potential importance of organoid models in developing innovative tumor-prevention techniques.
CURRENT MOLECULAR PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Mengqi Zhu, Jianping Zhang, Saiyan Bian, Xue Zhang, Yiping Shen, Zhiyu Ni, Shiyu Xu, Chun Cheng, Wenjie Zheng
Summary: This study aims to investigate the characteristics, prognostic significance, and targeted values of circadian genes in hepatocellular carcinoma (HCC). By analyzing the TCGA-LIHC database, abnormal expression of circadian genes was found to be associated with malignant clinicopathological characteristics of HCC patients. The circadian gene CSNK1D was further investigated and found to contribute to HCC progression by activating the Wnt/beta-catenin pathway.
BIOLOGICAL PROCEDURES ONLINE
(2022)
Review
Biochemistry & Molecular Biology
Jie Zhang, Lei Wang, Qianqian Song, Mingbing Xiao, Jie Gao, Xiaolei Cao, Wenjie Zheng
Summary: Environmental and genetic factors contribute to cancer development, and organoid models are a useful tool for studying the mechanisms of oncogenesis and developing targeted therapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)