Review
Pharmacology & Pharmacy
Dawid Dorna, Adriana Grabowska, Jaroslaw Paluszczak
Summary: Many natural products can exert anticancer or chemopreventive activity by interfering with the cellular epigenetic machinery, which can modulate cancer-related gene expression and functional changes, including reduced cell proliferation and migration, and enhanced apoptosis.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Bo Zhang, Chen Zhao, Wenchen Shen, Wei Li, Yue Zheng, Xiangfei Kong, Junbao Wang, Xudong Wu, Tao Zeng, Ying Liu, Yan Zhou
Summary: The hippocampus plays a crucial role in learning and memory, and its development requires precise coordination of cell patterning, proliferation, differentiation, and migration. In this study, it was found that KDM2B mediates a gene repressive program that controls fate specification and cell migration in the hippocampus, affecting its morphology and related behaviors.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Chunmin Guo, Mingy Zhao, Xinbin Sui, Zarin Balsara, Songhui Zhai, Michael Ahdoot, Yingshen Zhang, Christa M. Lam, Ping Zhu, Xue Li
Summary: Urinary tract infection (UTI) is a global health problem. Bladder infections induce expression of Ezh2, a methyltransferase, in bladder urothelial cells. Inactivation of Ezh2 improves outcomes of chronic and severe UTIs in mice, suggesting it as a potential non-antibiotic strategy for managing UTIs.
Article
Biochemistry & Molecular Biology
Ka-Wing Fong, Jonathan C. Zhao, Xiaodong Lu, Jung Kim, Andrea Piunti, Ali Shilatifard, Jindan Yu
Summary: PALI1 is a newly identified accessory protein that plays a role in advanced prostate cancer. It competes with JARID2 for binding to the PRC2 core subunit SUZ12 and interacts with the H3K9 methyltransferase G9A, forming a unique super-complex involved in dual H3K9/K27 methylation and gene repression. PALI1 and G9A promote prostate cancer cell proliferation and invasion, and drive tumor growth in xenograft models.
Article
Biochemistry & Molecular Biology
Junlong Zhao, Huichen Li, Shoujie Zhao, Enxin Wang, Jun Zhu, Dayun Feng, Yejing Zhu, Weijia Dou, Qingling Fan, Jie Hu, Lintao Jia, Lei Liu
Summary: The study uncovered novel mechanisms of miR-144/miR-451a cluster deregulation and the interaction between malignant cells and tumor-associated macrophages (TAMs) in HCC. This provides new insights into HCC pathogenesis and diagnostic strategies.
Review
Biochemistry & Molecular Biology
Gabriel Prado, Charlotte L. Kaestner, Jonathan D. Licht, Richard L. Bennett
Summary: Venetoclax, a BH-3 mimetic, can overcome certain forms of therapy resistance in hematologic malignancies, but other resistance mechanisms still exist. Recent studies show that targeting epigenetic mechanisms can disable oncogenic gene expression responsible for venetoclax resistance, and combination therapies with venetoclax and epigenetic therapies are effective in preclinical models.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Ali Seifinejad, Mergim Ramosaj, Ling Shan, Sha Li, Marie-Laure Possovre, Corinne Pfister, Rolf Fronczek, Lee A. Garrett-Sinha, David Frieser, Makoto Honda, Yoan Arribat, Dogan Grepper, Francesca Amati, Marie Picot, Andrea Agnoletto, Christian Iseli, Nicolas Chartrel, Roland Liblau, Gert J. Lammers, Anne Vassalli, Mehdi Tafti
Summary: Narcolepsy with cataplexy is caused by deficiency in the neuropeptide hypocretin/orexin (HCRT), believed to result from autoimmune destruction of hypocretin-producing neurons. Loss of hypothalamic CRH-producing neurons suggests that mechanisms other than autoimmune attack are involved. HCRT, PDYN, and CRH are epigenetically silenced by hypothalamic inflammation in narcolepsy patients, without concurrent cell death. Methylation reversal may lead to a potential cure for narcolepsy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Genetics & Heredity
Yiran Guo, Shuai Zhao, Gang Greg Wang
Summary: The modulation of chromatin structure and/or modification by Polycomb repressive complexes (PRCs) plays a crucial role in partitioning the genome and regulating gene activity. PRC2 enzymatic activity and its interaction with cofactors, DNA elements, histones, RNA, and effectors such as canonical PRC1 are intricately regulated to mediate gene silencing through mechanisms like chromatin compaction and histone deacetylation. Understanding the structural architecture and regulation of PRC2, as well as the molecular mechanisms of Polycomb-mediated gene silencing, has significant implications in biology and medicine.
TRENDS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Lu Gan, Qingguo Li, Wei Nie, Yi Zhang, Hesheng Jiang, Cong Tan, Long Zhang, Jieyun Zhang, Qian Li, Pengcong Hou, Yitao Yuan, Xun Sun, Dongmei Liu, Weiqi Sheng, Tianshu Liu, Midie Xu, Weijian Guo
Summary: PROX1 is a transcription factor that promotes malignant transformation and stemness in colorectal cancer (CRC). It has been found that PROX1 is associated with cell glucose metabolism and regulates cell proliferation and glucose metabolism through interaction with SIRT3. High PROX1 expression combined with low SIRT3 expression predicts poor prognosis in CRC patients.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Julian Aldana, Miranda L. L. Gardner, Michael A. A. Freitas
Summary: A comprehensive multi-omics approach was used to study the effects of differential H3K27me3 deposition driven by EZH2 mutations. The study identified pathways involved in cellular proliferation, differentiation, and migration that are impacted by EZH2 GOF and LOF mutants. The results shed light on EZH2-mediated cell transformative processes from the epigenetic to the phenotypic level, providing insights for improved diagnostics and treatment in hematologic malignancies with mutated EZH2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Xiaohua Luo, Ci Pan, Xiaopei Guo, Cunhua Gu, Yulian Huang, Jing Guo, Ying Zeng, Jinjing Yue, Shihong Cui
Summary: This study explores the role of miR-155 in the inflammatory pathogenesis of preeclampsia. Results show that the methylation levels of miR-155 are correlated with the inflammatory response in placental tissue. Overexpression of miR-155 inhibits trophoblast cell viability and migration, while inhibition of miR-155 suppresses inflammation and oxidative stress, while promoting cell proliferation and migration.
MEDIATORS OF INFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Zhongwei Li, Bingheng Li, Haiyuan Yu, Pengfei Wang, Wenwen Wang, Pingfu Hou, Minle Li, Sufang Chu, Junnian Zheng, Lijun Mao, Jin Bai
Summary: This study reveals the molecular interplay between DNA methyltransferase DNMT1 and histone methyltransferase EZH2 in the development and metastasis of prostate cancer. We found that high expression of DNMT1 promotes PC cell proliferation and migration by inhibiting TRAF6 transcriptional expression and TRAF6-mediated EZH2 ubiquitination. Our results also show that targeting DNMT1 with its inhibitor Decitabine can suppress tumor growth and metastasis through epigenetic regulation of DNMT1-mediated DNA methylation and EZH2-mediated histone methylation.
Article
Cell Biology
Xing Xu, Jun Chen, Yan Li, Xiaojie Yang, Qing Wang, Yanjun Wen, Ming Yan, Jianjun Zhang, Qin Xu, Yan Wei, Wantao Chen, Xu Wang
Summary: Through genomics, metabolomics, and RNA omics studies, it was discovered that inhibition of squalene epoxidase synergistically increased the sensitivity of HNSCC cells to EZH2 inhibitors, providing a basis for the development of new therapeutic strategies for HNSCC.
CELL DEATH & DISEASE
(2021)
Article
Medicine, Research & Experimental
Nuno Bastos, Stephanie A. Castaldo, Barbara Adem, Jose C. Machado, Carlos A. Melo, Sonia A. Melo
Summary: PDAC is driven by late diagnosis and inefficient therapies. By dissecting the mechanisms that regulate the expression of Rab27a and that control exosomes biogenesis, we can gain fundamental insights into the molecular underpinnings regulating PDAC progression.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Huitao Fan, Yiran Guo, Yi-Hsuan Tsai, Aaron J. Storey, Arum Kim, Weida Gong, Ricky D. Edmondson, Samuel G. Mackintosh, Haitao Li, Stephanie D. Byrum, Alan J. Tackett, Ling Cai, Gang Greg Wang
Summary: Trimethylation of histone H3 lysine 27 (H3K27me3) plays a crucial role in gene silencing and imprinting, (epi)genome organization, and organismal development. This study reveals that the Bromo Adjacent Homology (BAH) domain within BAH domain-containing protein 1 (BAHD1) is essential for the targeting of BAHD1 to chromatin and optimal repression of H3K27me3-demarcated genes in mammalian cells. Disruption of the direct interaction between BAHD1(BAH) and H3K27me3 leads to chromatin remodeling and increased histone acetylation at Polycomb gene targets, affecting embryonic development.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Health Care Sciences & Services
Fraide A. Ganotice, Amy Yin Man Chow, Kelvin Kai Hin Fan, Ui Soon Khoo, May Pui San Lam, Rebecca Po Wah Poon, Francis Hang Sang Tsoi, Michael Ning Wang, George L. Tipoe
Summary: The study showed that the Interprofessional Attitude Scale (IPAS) had good internal consistency and most of the confirmatory factor analysis results supported the overall five-factor solution. The various subscales of IPAS systematically correlated with other theoretically relevant variables such as teamwork attitudes, communication, and team effectiveness.
JOURNAL OF INTERPROFESSIONAL CARE
(2022)
Article
Oncology
Hyeon Gu Kang, Haeun Hwangbo, Myung Ji Kim, Sinae Kim, Eun Ji Lee, Min Ji Park, Jae-Weon Kim, Byoung-Gie Kim, Eun-Hae Cho, Suhwan Chang, Jung-Yun Lee, Jung Kyoon Choi
Summary: This study provides molecular and clinical evidence for transcriptional HRD (tHRD), which is associated with the response of cells to PARP inhibitors and genotoxic drugs. Machine learning-based detection of tHRD using the transcript usage (TU) pattern shows superior predictive accuracy compared to directly screening for BRCA1/2 mutations or gHRD. This approach has the potential to broaden the clinical utility of PARP inhibitors.
Review
Biochemistry & Molecular Biology
Chan-Ping You, Man-Hong Leung, Wai-Chung Tsang, Ui-Soon Khoo, Ho Tsoi
Summary: Biomarkers, such as estrogen receptor alpha(ER alpha), human epidermal growth factor receptor 2 (HER2), and androgen receptor (AR), have been widely used in breast cancer diagnosis, prognosis, and prediction. AR serves different roles in different breast cancer subtypes, acting as a tumor suppressor in ER+ breast cancers but a tumor promoter in ER- breast cancers. AR expression status can also predict the response to hormonal therapy and chemotherapy. Therefore, AR has the potential to be a useful biomarker in breast cancer.
Article
Biology
Ho Tsoi, Ling Shi, Man-Hong Leung, Ellen P. S. Man, Zi-Qing So, Wing-Lok Chan, Ui-Soon Khoo
Summary: A splice variant of NCOR2, called BQ, enhances tamoxifen resistance in ER+ breast cancer cells by modulating IL-8 expression. Targeting IL-8 signaling pathway is a promising approach to overcome tamoxifen resistance in ER+ breast cancer.
Article
Education, Scientific Disciplines
Fraide A. Ganotice, Linda Chan, Amy Yin Man Chow, Ui Soon Khoo, May Pui San Lam, Rebecca Ka Wai Liu, Rebecca Po Wah Poon, Michael Ning Wang, Francis Hang Sang Tsoi, George L. Tipoe
Summary: This study investigated the differences in attitudes and achievement between high-and low-performing teams in an online asynchronous and synchronous IPE program, and the role of autonomous motivation in determining team membership. High-performing teams were characterized by their recognition and endorsement of important interprofessional collaborative competencies, which was predicted by autonomous motivation.
NURSE EDUCATION TODAY
(2022)
Article
Oncology
Ho Tsoi, Chan-Ping You, Man-Hong Leung, Ellen P. S. Man, Ui-Soon Khoo
Summary: Breast cancer is a heterogeneous disease, and most cases are estrogen receptor-positive. However, many patients eventually develop resistance to the main treatment drug tamoxifen. Overexpression of c-MYC can drive the development of estrogen receptor-positive breast cancer and confer tamoxifen resistance. Ribosome biogenesis plays a crucial role in this process, and suppressing ribosome biogenesis may help reduce aggressiveness and reverse tamoxifen resistance. Some chemicals have been shown to repress ribosome biogenesis and may potentially reverse tamoxifen resistance in estrogen receptor-positive breast cancer. Identification of predictive markers will be necessary for the future use of these ribosome biogenesis inhibitors in combating tamoxifen resistance.
Article
Education, Scientific Disciplines
Fraide A. Ganotice, Sarah So Ching Chan, Amy Yin Man Chow, Kelvin Kai Hin Fan, Ui Soon Khoo, Ronnel B. King, May Pui San Lam, Pauline Luk, Alina Yee Man Ng, Michael Ning Wang, Susanna Siu-Sze Yeung, George L. Tipoe
Summary: This study investigated the independent contributions of team-level and student-level interprofessional attitudes to interprofessional education (IPE) collaboration outcomes. Results showed that teamwork, roles, and responsibilities were the best predictors of IPE outcomes, both at the student and team levels. Students who recognized the benefits of shared learning had better goal achievement and team effectiveness. Furthermore, teams that emphasized shared learning also had better overall team performance.
NURSE EDUCATION TODAY
(2022)
Article
Biochemistry & Molecular Biology
Ho Tsoi, Wai-Chung Tsang, Ellen P. S. Man, Man-Hong Leung, Chan-Ping You, Sum-Yin Chan, Wing-Lok Chan, Ui-Soon Khoo
Summary: This study reveals that tamoxifen treatment can enhance the expression of BQ in ER-positive breast cancer by activating the ATM/CHK2 axis. Targeting CHK2 is a promising approach to overcoming tamoxifen resistance in ER-positive breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Changxu Wang, Qilai Long, Qiang Fu, Qixia Xu, Da Fu, Yan Li, Libin Gao, Jianming Guo, Xiaoling Zhang, Eric W-F Lam, Judith Campisi, Yu Sun
Summary: The soluble factor EREG, produced by senescent stromal cells, plays a crucial role in the development and malignant progression of cancer cells in the tumor microenvironment. Targeting EREG in treatment-damaged TME significantly improves cancer therapeutic efficacy and shows potential value in translational medicine.
Article
Multidisciplinary Sciences
Philip Chiu-Tsun Tang, Jeff Yat-Fai Chung, Jinyue Liao, Max Kam-Kwan Chan, Alex Siu-Wing Chan, Guangyao Cheng, Chunjie Li, Xiao-Ru Huang, Calvin Sze -Hang Ng, Eric W. -F Lam, Dongmei Zhang, Yi-Ping Ho, Ka-Fai To, Kam -Tong Leung, Xiaohua Jiang, Ho Ko, Tin -Lap Lee, Hui-Yao Lan, Patrick Ming-Kuen Tang
Summary: This study discovered a direct mechanism of tumor-associated macrophage (TAM) for promoting de novo neurogenesis, which contributes to a better understanding of tumor innervation. The study also identified a phenomenon of macrophage to neuron-like cell transition (MNT) and identified a crucial regulator for MNT. This finding has potential clinical significance for the treatment of cancer pain.
Review
Biochemistry & Molecular Biology
Chan-Ping You, Ho Tsoi, Ellen P. S. Man, Man-Hong Leung, Ui-Soon Khoo
Summary: Activation of the androgen receptor (AR) can suppress disease progression in estrogen receptor alpha-positive breast cancer, while blocking AR might provide better prognosis in estrogen receptor alpha-negative breast cancer. Modulating AR activity could be a potential strategy for treating breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ho Tsoi, Nicholas Nok-Ching Fung, Ellen P. S. Man, Man-Hong Leung, Chan-Ping You, Wing-Lok Chan, Sum-Yin Chan, Ui-Soon Khoo
Summary: Overexpressing BQ can confer tamoxifen resistance in ER +ve breast cancer. BQ is an alternative splice variant of NCOR2 generated through the exclusion of exon 11. SRSF5 is involved in the regulation of NCOR2 splicing. Low expression of SRSF5 increases the production of BQ mRNA by excluding exon 11. Thus, targeting the upstream pathway of BQ may reverse tamoxifen resistance.
Article
Multidisciplinary Sciences
Weiyingqi Cui, Ning Xie, Eric W. -F. Lam, Victoria Hahn-Stromberg, Na Liu, Hong Zhang, Xiao-Feng Sun
Summary: Accumulating evidence suggests the important roles of FOXO3, FOXM1, and SIRT6 in cancer progression. This study investigates the expression and clinical significance of these proteins in rectal cancer patients undergoing radiotherapy (RT). The results show that FOXO3 and FOXM1 are mainly expressed in the cytoplasm, while SIRT6 is expressed in both the cytoplasm and nucleus. FOXO3 expression increases with tumor progression, while SIRT6 expression decreases. High FOXO3 expression is associated with late TNM stage, distant metastasis, and poor prognosis in RT patients. Genetic analysis implicates DNA methylation in FOXO3 overexpression. Functional enrichment analysis reveals the involvement of FOXO3 in metabolism-related signaling pathways and radioresistance. In conclusion, FOXO3 may serve as a prognostic factor in rectal cancer patients undergoing RT.
Article
Oncology
Ho Tsoi, Johann Lok, Ellen P. S. Man, Cheuk-Nam Cheng, Man-Hong Leung, Chan-Ping You, Sum-Yin Chan, Wing-Lok Chan, Ui-Soon Khoo
Summary: This study revealed that overexpression of a novel splice variant BQ323636.1 is associated with resistance to the non-steroidal aromatase inhibitor anastrozole in ER+ post-menopausal breast cancer. Mechanistic studies showed that BQ overexpression enhances androgen receptor (AR) activity, leading to hyper-activation of AR signaling and increased cell proliferation. Targeting AR can overcome anastrozole resistance in breast cancer with BQ overexpression. Clinical study also demonstrated that high nuclear expression of both BQ and AR is significantly associated with poor survival in non-steroidal aromatase inhibitor-treated ER+ breast cancer patients.
JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eun Ji Lee, Seung-Jae Noh, Huiseon Choi, Min Woo Kim, Su Jin Kim, Yeon Ah Seo, Ji Eun Jeong, Inkyung Shin, Jong-Seok Kim, Jong-Kwon Choi, Dae-Yeon Cho, Suhwan Chang
Summary: This study used RNA-seq analysis to investigate the changes in splicing patterns and correlations of tissue-specific genes during primary-patient derived xenograft (PDX) tumor formation. The results revealed significant changes in splicing patterns and overall strong positive correlations between primary and PDX tumors, except for gastric cancer cases. These findings suggest that tissue specificity and splicing events may play a role in primary-PDX integrity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)