Article
Biochemistry & Molecular Biology
Lin Zheng, Hui Liang, Qiaoling Zhang, Zichu Shen, Yixin Sun, Xuyang Zhao, Jingjing Gong, Zhiyuan Hou, Kewei Jiang, Quan Wang, Yan Jin, Yuxin Yin
Summary: This study revealed a novel circular RNA (circPTEN1) generated from the PTEN gene, which is downregulated in colorectal cancer and associated with poor survival. Low expression of circPTEN1 promotes metastasis and invasion, while overexpression shows opposite effects. Mechanistically, circPTEN1 binds to Smad4 and disrupts its interaction with Smad2/3, inhibiting the formation and translocation of Smad complexes. Additionally, eIF4A3 suppresses the cyclization of circPTEN1.
Article
Oncology
Justin Joseph, Capucine R. Magaut, Simon Storevik, Luiz H. Geraldo, Thomas Mathivet, Md Abdul Latif, Justine Rudewicz, Joris Guyon, Matteo Gambaretti, Frida Haukas, Amalie Trones, Lars A. Romo Ystaas, Jubayer A. Hossain, Sandra Ninzima, Sylvain Cuvellier, Wenjing Zhou, Tushar Tomar, Barbara Klink, Lalit Rane, Bronwyn K. Irving, Joanne Marrison, Peter O'Toole, Heiko Wurdak, Jian Wang, Zhang Di, Even Birkeland, Frode S. Berven, Frank Winkler, Frank A. E. Kruyt, Andreas Bikfalvi, Rolf Bjerkvig, Thomas Daubon, Hrvoje Miletic
Summary: Analysis of TCGA data revealed a high activation of the TGF-beta pathway in GBMs compared to oligodendroglial tumors. Stimulation of GBM cell lines with TGF-beta 1 enhanced MT formation and communication via calcium signaling, while inhibition of the TGF-beta pathway significantly reduced MT formation and invasion. Downstream of TGF-beta, thrombospondin 1 (TSP1) was identified as a potential mediator of MT formation in GBM, which was upregulated upon TGF-beta stimulation and inhibited MT formation when knocked down in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Antonio Tejera-Munoz, Laura Marquez-Exposito, Lucia Tejedor-Santamaria, Sandra Rayego-Mateos, Macarena Orejudo, Beatriz Suarez-Alvarez, Carlos Lopez-Larrea, Marta Ruiz-Ortega, Raul R. Rodrigues-Diez
Summary: CCN2 plays a role in both fibrotic responses and growth factor-induced oxidative and proinflammatory responses. Its coexistence with TGF-β is necessary for persistent fibrotic response, but the mechanisms involved are not fully understood. CCN2 increases T beta RII expression in VSMCs and maintains TGF-β pathway activation through an EGFR-SMAD dependent manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hua-fei Deng, Jiang Zou, Nian Wang, Heng Ma, Li-li Zhu, Ke Liu, Mei-dong Liu, Kang-Kai Wang, Xian-zhong Xiao
Summary: This study demonstrates that nicorandil can alleviate myocardial remodeling post-MI by promoting autophagy and regulating the TGF-beta/Smad signaling pathway through up-regulating nucleolin expression.
CELLULAR SIGNALLING
(2022)
Article
Developmental Biology
Sarah S. McCarthy, Michele Karolak, Leif Oxburgh
Summary: Expansion of interstitial cells in adult kidney is a hallmark of chronic disease, while their proliferation during fetal development is necessary for organ formation. Inactivation of TGF beta/Smad response in mouse interstitial cell lineage leads to overproliferation of interstitial cells regionally in the kidney medulla. Smad4 loss primarily reduces TGF beta signaling in the interstitium, while increasing Wnt/beta-catenin signaling.
Article
Chemistry, Multidisciplinary
Min Hou, Rui Guo, Tianyu Ren, Tao Wang, Jian-Hui Jiang, Jianjun He
Summary: This study reports the use of a DNA thalidomide conjugate (PASTE) to selectively bind and induce proteolysis of targeted activated transcription factor (PROTAF), providing a potential tool for studying signaling pathways and developing precision medicines.
Article
Biotechnology & Applied Microbiology
Yufei Qiu, Xudong Song, Yong Liu, Yan Wu, Jiayi Shi, Fan Zhang, Yu Pan, Zhiqin Cao, Keke Zhang, Jingruo Liu, Yanhui Chu, Xiaohuan Yuan, Dan Wu
Summary: Cardiac fibrosis is a remodeling process characterized by abnormal metabolism of the extracellular matrix and excessive accumulation of collagen fibers. Transforming growth factor-beta 1 (TGF-beta 1) plays a crucial role in this process. Studies have shown that interfering with TGF-beta 1 and its signaling pathways using latency-associated peptide (LAP) can attenuate cardiac fibrosis. In this study, recombinant LAP and truncated LAP were found to inhibit activation, inflammation, and fibrosis in isoproterenol-induced cardiac fibroblasts, and also improved cardiac function and alleviated myocardial injury, inflammation, and fibrosis in mice.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Cell Biology
Zhigang Yi, Tao Ma, Jia Liu, Wenting Tie, Yanhong Li, Jun Bai, Lijuan Li, Liansheng Zhang
Summary: This study found that LGR4 expression was significantly upregulated in multiple myeloma (MM) tissues and cells. Knockdown of LGR4 inhibited MM cell proliferation, promoted apoptosis and cell cycle arrest in G1, while overexpression showed the opposite effect. Mechanistic studies revealed that LGR4 could interact with TGF-beta 1 and activate the TGF-beta 1/Smad signaling pathway, promoting MM progression. LGR4 may be a potential new target for MM diagnosis and treatment.
CELLULAR SIGNALLING
(2023)
Article
Orthopedics
Nathalie G. M. Thielen, Arjan P. M. van Caam, Henk M. V. Beuningen, Elly L. Vitters, Martijn H. J. van den Bosch, Marije I. Koenders, Fons A. J. van de Loo, Esmeralda N. Blaney Davidson, Peter M. van der Kraan
Summary: The study aimed to block TGF-beta-induced SMAD1/5/9 signaling in primary human OA chondrocytes while maintaining functional SMAD2/3 signaling. The results demonstrated that using a low dose of SB-505124 inhibited SMAD1/5/9 phosphorylation and the expression of ID1 and ID3, while maintaining SMAD2/3 phosphorylation and the induction of JUNB and SERPINE1. In addition, TGF-beta regulated hypertrophic and dedifferentiation markers in OA chondrocytes, and blocking only the SMAD1/5/9 pathway showed stronger inhibition on TGF-beta-induced RUNX2 compared to blocking both SMAD pathways.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Review
Cell Biology
Lih-Fhung Hiew, Chi-Him Poon, Heng-Ze You, Lee-Wei Lim
Summary: Research on TGF-beta/Smad signaling has shown its significance in neurogenesis and its potential impact on neuropsychiatric disorders. The relationship between TGF-beta/Smad signaling and neurogenesis in response to stressors suggests a role in stress response regulation and behavioral outcomes of mood disorders. Modifications to these signaling pathways have been found to have diverse effects on neurogenesis, highlighting the complexity of the interactions involved.
Article
Oncology
Eddie Luidy Imada, Diego Fernando Sanchez, Wikum Dinalankara, Thiago Vidotto, Ericka M. Ebot, Svitlana Tyekucheva, Gloria Regina Franco, Lorelei Ann Mucci, Massimo Loda, Edward Matthew Schaeffer, Tamara Lotan, Luigi Marchionni
Summary: In this study, a transcriptional signature of PTEN loss in prostate cancer was identified, showing activation of immune systems and cell-cycle genes. The study also discovered potential novel lncRNAs associated with PTEN loss and prostate cancer progression, expanding the understanding of the molecular landscape in PCa. The findings suggest that PTEN loss in prostate cancer leads to increased immune system activation, contrary to observations in other cancers, which could have implications for the development of biomarkers and therapy choices.
Article
Medicine, Research & Experimental
Alex Boye
Summary: Early detection of cancer is crucial for cancer management and limited survival. Understanding cancer biology and key factors in cancer progression plays a significant role in cancer treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Chunjun Li, Xiangxiang Meng, Lina Wang, Xia Dai
Summary: Cardiac fibrosis is a serious global public health problem associated with the progression of cardiovascular diseases. The TGF-beta/Smad signaling pathway plays a key role in cardiac fibrosis, and targeted inhibition of this pathway may be a therapeutic approach. Traditional Chinese Medicine (TCM) has also been found to modulate multiple targets and signaling pathways, including TGF-beta/Smad, in the treatment of cardiac fibrosis. This article summarizes the roles of TGF-beta/Smad signaling pathways and discusses recent research on ncRNAs and TCM as potential treatments for cardiac fibrosis.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Naohiro Nakamura, Katsunori Yoshida, Rinako Tsuda, Miki Murata, Takashi Yamaguchi, Kanehiko Suwa, Mayuko Ichimura, Koichi Tsuneyama, Koichi Matsuzaki, Toshiaki Nakano, Junko Hirohara, Toshihito Seki, Kazuichi Okazaki, M. Eric Gershwin, Makoto Naganuma
Summary: Patients with primary biliary cholangitis (PBC) are at higher risk for developing hepatocellular carcinoma (HCC), especially in the presence of comorbidities like excessive alcohol consumption. This study found that the balance of Smad signals may serve as a biomarker to predict the likelihood of HCC occurrence in PBC patients. Shifting favorably Smad phospho-isoforms through therapies could potentially reduce the risk of PBC-related HCC development.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2021)
Article
Cardiac & Cardiovascular Systems
Bijun Chen, Ruoshui Li, Silvia C. Hernandez, Anis Hanna, Kai Su, Arti V. Shinde, Nikolaos G. Frangogiannis
Summary: TGF-beta signaling through Smad2/3 regulates macrophage responses in myocardial infarction. Smad3 plays a crucial role in mediating the anti-inflammatory and phagocytic effects of TGF-beta, while the activation of Smad2 does not affect these processes. Smad3, but not Smad2, is the main mediator of transcriptional effects of TGF-beta on macrophages.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lidong Sun, Kenji Kokura, Victoria Izumi, John M. Koomen, Edward Seto, Jiandong Chen, Jia Fang
Article
Cell Biology
Lidong Sun, Jia Fang
Review
Biochemistry & Molecular Biology
Lidong Sun, Jia Fang
CELLULAR AND MOLECULAR LIFE SCIENCES
(2016)
Article
Biochemistry & Molecular Biology
Lidong Sun, Jia Fang
Article
Cell Biology
Yonglei Liu, Chuanzhong Mei, Lidong Sun, Xin Li, Mingzhu Liu, Liying Wang, Zengxia Li, Peng Yin, Chao Zhao, Yinghong Shi, Shuangjian Qiu, Jia Fan, Xiliang Zha
CELLULAR SIGNALLING
(2011)
Article
Chemistry, Medicinal
Hong Jia, Guangxiu Dai, Jianyang Weng, Zhulin Zhang, Qing Wang, Feng Zhou, Longxian Jiao, Yumin Cui, Yongxin Ren, Shiming Fan, Jinghong Zhou, Weiguo Qing, Yi Gu, Jian Wang, Yang Sai, Weiguo Su
JOURNAL OF MEDICINAL CHEMISTRY
(2014)
Article
Oncology
Paul R. Gavine, Yongxin Ren, Lu Han, Jing Lu, Shiming Fan, Wei Zhang, Wen Xu, Yuan Jie Liu, Tianwei Zhang, Haihua Fu, Yongjuan Yu, Huiying Wang, Shirlian Xu, Feng Zhou, Xinying Su, XiaoLu Yin, Liang Xie, Linfang Wang, Weiguo Qing, Longxian Jiao, Weiguo Su, Q. May Wang
MOLECULAR ONCOLOGY
(2015)
Article
Multidisciplinary Sciences
Diancai Zhang, Jianbin Xiang, Liying Wang, Zhibin Xu, Lidong Sun, Feng Zhou, Xiliang Zha, Duan Cai
Article
Cell Biology
Tanjing Song, Qingli Zou, Yingying Yan, Suli Lv, Neng Li, Xuefeng Zhao, Xianyun Ma, Haigang Liu, Borui Tang, Lidong Sun
Summary: DOT1L protein stability is regulated by extracellular glucose levels through the HBP pathway. O-GlcNAcylation and UBE3C are critical determinants of DOT1L protein abundance, affecting cell proliferation and histone H3K79 methylation in MLL-fusion leukemia.
Review
Cell Biology
Tanjing Song, Suli Lv, Neng Li, Xuefeng Zhao, Xianyun Ma, Yingying Yan, Weixia Wang, Lidong Sun
Summary: m6A machinery, a crucial RNA modification mechanism, is involved in the regulation of RNA processing and function. Recent studies have demonstrated that m6A machinery can be recruited to chromatin by various factors, leading to direct regulation of chromatin biology such as transcription, DNA damage repair, and DNA recombination.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Suli Lv, Xuefeng Zhao, Erlei Zhang, Yingying Yan, Xianyun Ma, Neng Li, Qingli Zou, Lidong Sun, Tanjing Song
Summary: This study identifies a functional KDM1A-FKBP8-BCL2 axis in hepatocellular carcinoma (HCC), showing that KDM1A can demethylate FKBP8 to enhance the stability of BCL2, promoting HCC cell growth. The cytoplasmic localization of KDM1A is regulated by acetylation at lysine-117 by KAT8. In addition, the study reveals that KDM1A and BCL2 protein levels increase during acquired sorafenib resistance and inhibiting KDM1A can antagonize this resistance.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Suli Lv, Xuefeng Zhao, Xianyun Ma, Qingli Zou, Neng Li, Yingying Yan, Lidong Sun, Tanjing Song
Summary: RfxCas13d is an RNA-guided RNA endonuclease that can knockdown gene expression with high specificity. In this study, we investigated the mechanism of its inducible knockdown and designed an all-in-one Cas13d lentivirus vector that allows efficient and inducible knockdown depending on the dosage of doxycycline. Furthermore, we found that Cas13d has a short half-life in mammalian cells, allowing prompt restoration of knockdown after doxycycline withdrawal. This research has significant implications for future applications.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tanjing Song, Suli Lv, Xianyun Ma, Xuefeng Zhao, Li Fan, Qingli Zou, Neng Li, Yingying Yan, Wen Zhang, Lidong Sun
Summary: TRIM28 inhibits autophagy to suppress kidney cancer cell proliferation. TFE3 activates autophagic gene expression and interacts with histone demethylase KDM6A to upregulate autophagic genes. This study identifies a critical signaling axis in kidney cancer cell autophagy and proliferation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Oncology
Feng Zhou, Guimei Yang, Liting Xue, Yajing Liu, Yao Guo, Ji Zhu, Linlin Yuan, Peng Gu, Feng Tang, Jinwen Shan, Renhong Tang
Summary: SCR-6852 is a novel SERD that exhibits high potency in inducing ERα protein degradation and pure antagonistic activity on ERα signaling both in vitro and in vivo. Due to its high brain penetrability, SCR-6852 could be used to treat breast cancer patients with brain metastasis.
BREAST CANCER RESEARCH
(2023)
Review
Oncology
Lidong Sun, Suli Lv, Tanjing Song
Summary: Prevalent dysregulation of epigenetic modifications plays a pivotal role in cancer. O-GlcNAcylation, a protein modification that affects physiology and pathophysiology, is closely related to epigenetic modifications, and oncogenic signals regulate epigenetic abnormalities in cancer by modulating O-GlcNAcylation dysregulation.
