Review
Cell Biology
Albano Toska, Nikita Modi, Lin-Feng Chen
Summary: RUNX3 is a transcription factor involved in cell proliferation and development. It can act both as a tumor suppressor and an oncogene in different cancers. The tumor suppressor function of RUNX3 is mainly attributed to its ability to suppress cancer cell proliferation through ubiquitination and proteasomal degradation, while it can also be inactivated through the same mechanism.
Article
Cell Biology
Feng Zhang, Tao Su, Meifang Xiao
Summary: This study investigated the function of circMETTL3/miR-107/PER3 in colorectal cancer (CRC). The findings suggest that circMETTL3, transcriptionally activated by RUNX3, acts as a sponge for miR-107 to regulate PER3 signaling, thereby inhibiting CRC cell proliferation and invasion and restraining tumor growth and metastasis.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Naizhi Sun, Jiacheng Shen, Yuhua Shi, Biao Liu, Shengguo Gao, Yichuan Chen, Jinwei Sun
Summary: This study aimed to investigate the molecular mechanisms of TRIM58 in colorectal cancer (CRC) development. TRIM58 is an E3 ubiquitin ligase and a potential prognostic marker for cancer. The study found that TRIM58 acts as a tumor suppressor in CRC by promoting RECQL4 ubiquitination and inhibiting the AKT signaling pathway, suggesting it could be a potential target for CRC treatment.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Ying Zhao, Jing Ruan, Zhongding Li, Xian Su, Kangmin Chen, Yimin Lin, Yuepiao Cai, Peng Wang, Baohua Liu, Dirk Schlueter, Guang Liang, Xu Wang
Summary: This study reveals that CCN6 protein levels in breast cancer are regulated by ubiquitination and deubiquitinating enzymes (DUBs). OTUB1 is identified as a novel DUB for CCN6 and inhibits its degradation by interacting with CCN6 and inhibiting its K48 ubiquitination. Deletion of OTUB1 results in decreased CCN6 abundance and increased migration, proliferation, and viability of breast cancer cells, which can be rescued by supplementation of CCN6. Importantly, OTUB1 expression is downregulated in human breast cancer and positively correlated with CCN6 levels.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Mi-Jeong Kim, Yoon Min, Soo-Kyung Jeong, Juhee Son, Ji Young Kim, Ji Su Lee, Duk-Hwan Kim, Joo Sang Lee, Eunyoung Chun, Ki-Young Lee
Summary: The study reveals that USP15 is significantly downregulated in lung cancer patients, and its knockout leads to increased migration, invasion, and autophagy induction in lung cancer cells. USP15 interacts with BECN1 and deubiquitinates it, thereby attenuating autophagy induction. Additionally, the expression of USP15 is associated with the upregulation of certain oncogenes and downregulation of tumor suppressor genes in lung cancer patients.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Yanwei Luo, Xinye Wang, Weihong Niu, Yao Zhou, Mengna Li, Jinqi Ma, Jing Yang, Songqing Fan, Zhaoyang Zeng, Wei Xiong, Xiaoling Li, Guiyuan Li, Jidong Xiao, Ming Zhou
Summary: BRD7 functions as a tumor suppressor in breast cancer by stabilizing p53 through inhibiting the phosphorylation of MDM2, and regulating the expression of p53 downstream target genes.
Article
Cell Biology
Kailing Zhou, Yu Sun, Dan Dong, Chenghai Zhao, Wei Wang
Summary: EMP3 acts as a potential tumor suppressor in breast cancer by inhibiting cell cycle progression, DNA repair, and stem-like properties, leading to enhanced sensitivity of breast cancer cells to DNA-damaging agents.
CELL DEATH & DISEASE
(2021)
Article
Environmental Sciences
Hai Qin, Yaqin Yuan, Manqin Yuan, Haiyan Wang, Yonghong Yang
Summary: This study found that AZGP1 was highly expressed in breast cancer and negatively correlated with patient survival. Functional experiments showed that AZGP1 can promote the proliferation, migration, and invasion ability of breast cancer cells. Mechanistically, it was found that AZGP1 interacted with TRIM25 and was degraded through ubiquitination.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sun Hee Lee, Do Young Hyeon, Soo-Hyun Yoon, Ji-Hak Jeong, Saeng-Myung Han, Ju-Won Jang, Minh Phuong Nguyen, Xin-Zi Chi, Sojin An, Kyung-gi Hyun, Hee-Jung Jung, Ji-Joon Song, Suk-Chul Bae, Woo-Ho Kim, Daehee Hwang, You Mie Lee
Summary: Under hypoxic conditions, G9a-mediated methylation regulates the inactivation of RUNX3, promoting cancer cell proliferation and suppressing immune response and apoptosis, thereby facilitating tumor growth during early tumorigenesis.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Oncology
Sehbanul Islam, Parul Dutta, Osheen Sahay, Kesavaperumal Gopalakrishnan, Sushrita Roy Muhury, Parinitha Parameshwar, Praveenkumar Shetty, Manas Kumar Santra
Summary: The oncogene c-Myc suppresses the expression of FBXO31 in ovarian cancer, impairing its tumor-suppressive functions. In contrast, FBXO31 degrades c-Myc through the proteasome pathway, inhibiting ovarian cancer growth. The c-Myc-FBXO31 axis shows promise as a target for developing better cancer therapies.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Chemistry, Multidisciplinary
Mahmoud Alhosin, Omeima Abdullah, Asaad Kayali, Ziad Omran
Summary: The study demonstrates that TQ can induce ubiquitination of UHRF1 in cancer cells through downregulation of HAUSP, leading to therapeutic effects. Similar to TQ, doxorubicin also causes downregulation of UHRF1 in cancer cells, but without ubiquitination.
APPLIED SCIENCES-BASEL
(2021)
Article
Cell Biology
Evangelos Prokakis, Shaishavi Jansari, Angela Boshnakovska, Maria Wiese, Kathrin Kusch, Christof Kramm, Christian Dullin, Peter Rehling, Markus Glatzel, Klaus Pantel, Harriet Wikman, Steven A. Johnsen, Julia Gallwas, Florian Wegwitz
Summary: This study identifies the essential role of RNF40 in supporting the aggressive behavior of triple-negative breast cancer by regulating gene transcription and promoting specific signaling pathways. Targeting RNF40 may have high therapeutic value in combating the malignant behavior of TNBC.
CELL DEATH & DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Aiqin Sun, Yifei Chen, Xianyan Tian, Qiong Lin
Summary: This article summarizes the role of HECT E3 ligases in colorectal carcinogenesis and the underlying molecular mechanisms. Targeting HECT E3 ligases with specific inhibitors could be a potential therapeutic strategy for colorectal cancer in the future.
Article
Biochemistry & Molecular Biology
Xiaofeng Jin, Shi Qing, Qian Li, Hui Zhuang, Liliang Shen, Jinhui Li, Honggang Qi, Ting Lin, Zihan Lin, Jian Wang, Xinyi Cao, Jianye Yang, Qi Ma, Linghua Cong, Yang Xi, Shuai Fang, Xiaodan Meng, Zhaohui Gong, Meng Ye, Shuyun Wang, Chenji Wang, Kun Gao
Summary: SPOP protein is phosphorylated by ATM kinase upon DNA damage, enhancing its binding to HIPK2 and facilitating DNA damage repair. This process is disrupted by SPOP mutations in prostate cancer, leading to genomic instability.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Sujitha Jayaprakash, Mangala Hegde, Bandari BharathwajChetty, Sosmitha Girisa, Mohammed S. Alqahtani, Mohamed Abbas, Gautam Sethi, Ajaikumar B. Kunnumakkara
Summary: Cancer is a deadly disease that is strongly related to genetic changes and post-translational modifications. The E3 ubiquitin ligases, particularly NEDD4, play a crucial role in regulating cellular processes by controlling protein degradation and substrate ubiquitination. NEDD4 has both tumor-suppressive and oncogenic roles in various malignancies. This review summarizes the function of NEDD4 in cancer development, including its role in cell survival, proliferation, autophagy, migration, invasion, metastasis, epithelial-mesenchymal transition, chemoresistance, and multiple signaling pathways. Additionally, the significance of NEDD4 as a potential target for cancer treatment is discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Maurice B. Loughrey, Jason McGrath, Helen G. Coleman, Peter Bankhead, Perry Maxwell, Claire McGready, Victoria Bingham, Matthew P. Humphries, Stephanie G. Craig, Stephen McQuaid, Manuel Salto-Tellez, Jacqueline A. James
Summary: This study compared PCR-based microsatellite instability (MSI) testing and MMR protein immunohistochemistry (IHC) in colorectal cancer cases and found that both methods are equally proficient in establishing MMR/MSI status, but awareness of potential pitfalls is important. The choice of methodology may depend on available services and expertise.
Article
Biochemistry & Molecular Biology
M. P. Humphries, P. Maxwell, M. Salto-Tellez
Summary: QuPath, created at Queen's University Belfast, is the most widely used image analysis software program globally, addressing various needs in tissue-based image analysis and serving as the system of choice for researchers in scientific research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Gastroenterology & Hepatology
Jonathan W. J. Lee, Feng Zhu, Supriya Srivastava, Stephen Kk Tsao, Christopher Khor, Khek Yu Ho, Kwong Ming Fock, Wee Chian Lim, Tiing Leong Ang, Wan Cheng Chow, Jimmy Bok Yan So, Calvin J. Koh, Shijia Joy Chua, Andrew S. Y. Wong, Jaideepraj Rao, Lee Guan Lim, Khoon Lin Ling, Chung-King Chia, Choon Jin Ooi, Andrea Rajnakova, Wai Ming Yap, Manuel Salto-Tellez, Bow Ho, Richie Soong, Kee Seng Chia, Yik Ying Teo, Ming Teh, Khay-Guan Yeoh
Summary: This study found that gastric intestinal metaplasia (IM) is a significant risk factor for early gastric neoplasia (EGN) in regions with low-intermediate incidence of gastric cancer. Based on the results, it is recommended that high-risk patients (OLGIM III-IV) undergo endoscopic surveillance every 2 years, and intermediate-risk patients (OLGIM II) every 5 years.
Article
Pathology
Ross J. Porter, Graeme Murray, Abdo Alnabulsi, Matthew P. Humphries, Jacqueline A. James, Manuel Salto-Tellez, Stephanie G. Craig, Ji M. Wang, Teizo Yoshimura, Mairi H. McLean
Summary: Research reveals that loss of cathelicidin is associated with human CRC progression, with a switch in expression intensity as an early feature. LL-37 expression intensity is linked to CD8(+) T cell infiltrate and influenced by tumor characteristics.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2021)
Article
Oncology
Stephanie G. Craig, Svenja Mende, Matthew P. Humphries, Victoria Bingham, Amelie Viratham Pulsawatdi, Maurice B. Loughrey, Helen G. Coleman, Stephen McQuaid, Richard H. Wilson, Sandra Van Schaeybroeck, Jacqueline A. James, Manuel Salto-Tellez
Summary: Clinical trials on MET inhibitors for colon cancer have shown limited success, potentially due to lack of standardisation in MET assessment. This study identified a high-risk subgroup with high MET RNA-ISH/low c-MET IHC protein expression associated with poor outcomes, suggesting the need for subtyping of MET expression to identify patients who will benefit from MET inhibition.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Md Mostafa Kamal Sarker, Yasmine Makhlouf, Stephanie G. Craig, Matthew P. Humphries, Maurice Loughrey, Jacqueline A. James, Manuel Salto-Tellez, Paul O'Reilly, Perry Maxwell
Summary: This study proposes a AI-based workflow using deep learning for cell segmentation/detection in IHC slides to quantify nuclear staining biomarkers like ICOS. It consists of a simplified but robust annotation process and cell segmentation/detection models, providing an optimized workflow with a new user-friendly tool.
Article
Oncology
Eileen E. Parkes, Matthew P. Humphries, Elaine Gilmore, Fatima A. Sidi, Victoria Bingham, Su M. Phyu, Stephanie Craig, Catherine Graham, Joseph Miller, Daryl Griffin, Manuel Salto-Tellez, Stephen F. Madden, Richard D. Kennedy, Samuel F. Bakhoum, Stephen McQuaid, Niamh E. Buckley
Summary: The study introduces a new method to assess STING activation in tumor cells, showing that pnSTING expression is associated with good prognosis in ER+ breast cancer but not in ER- disease. Additionally, low pnSTING is linked to chromosomal instability, MYC amplification, and mTOR signaling.
Article
Pathology
Abdo Alnabulsi, Tiehui Wang, Wei Pang, Marius Ionescu, Stephanie G. Craig, Matthew P. Humphries, Kris McCombe, Manuel Salto Tellez, Ayham Alnabulsi, Graeme Murray
Summary: A study developed an effective methodology to identify optimal biomarker combinations for the prognosis of colorectal carcinoma. Six biomarkers were identified as the best combination in terms of prognostic power, and it was significantly associated with overall survival and independent of other clinicopathological parameters. The study also demonstrated the potential of this methodology for biomarker discovery in various biological and clinical studies.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2022)
Article
Oncology
Vivek Kumar Singh, Md Mostafa Kamal Sarker, Yasmine Makhlouf, Stephanie G. Craig, Matthew P. Humphries, Maurice B. Loughrey, Jacqueline A. James, Manuel Salto-Tellez, Paul O'Reilly, Perry Maxwell
Summary: In this study, a lightweight deep learning model called ICOSeg is proposed to accurately segment the immune-checkpoint biomarker ICOS protein in colon cancer immunohistochemistry slide patches. The proposed model utilizes a convolutional neural network and transformer to extract relevant features from immunohistochemistry images and performs segmentation using an encoder and decoder sub-network. Experimental results show that ICOSeg achieves better segmentation results compared to existing methods with a reduction in parameters.
Article
Pathology
Matthew Phillip Humphries, Victoria Bingham, Fatima Abdullah Sidi, Stephanie Craig, Beatrize Lara, Hesham El-daly, Nicole O'Doherty, Perry Maxwell, Claire Lewis, Stephen McQuaid, James Lyness, Jacqueline James, David R. J. Snead, Manuel Salto-Tellez
Summary: In this study, a validated protocol using multiplex immunofluorescence (mIF) was described for the exploration of the molecular physiopathology of SARS-CoV-2 pulmonary disease. Validated assays originally developed for the detection of SARS-CoV-2 in tissues were applied to map the adaptive immune response at protein and mRNA levels. The mIF panels showed robust, reliable, and quantifiable performance in detecting topographic variations in inflammation related to pathological processes in formalin-fixed, paraffin-embedded pneumonia material.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Editorial Material
Oncology
Manuel Salto-Tellez, Jorge S. Reis-Filho
Review
Biochemistry & Molecular Biology
Alice Geaney, Paul O'Reilly, Perry Maxwell, Jacqueline A. James, Darragh Mcart, Manuel Salto-Tellez
Summary: Digital pathology and artificial intelligence have transformed oncology research and cancer diagnostics, allowing for better interpretation of pathology images and improved quantitation of biomarkers. Different approaches of artificial intelligence can solve various problems in pathology workflows and have the potential to revolutionize clinical trials and create complex biomarkers for cancer patients.
Article
Biochemistry & Molecular Biology
Kris D. McCombe, Stephanie G. Craig, Amelie Viratham Pulsawatdi, Javier I. Quezada-Marin, Matthew Hagan, Simon Rajendran, Matthew P. Humphries, Victoria Bingham, Manuel Salto-Tellez, Richard Gault, Jacqueline A. James
Summary: The growth of digital pathology has led to advancements in cancer prediction and prognosis research through the use of deep learning and computer vision techniques. HistoClean, a user-friendly application, aims to improve deep learning models by providing transparent image pre-processing and augmentation techniques.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
A. Stupnikov, C. E. McInerney, K. I. Savage, S. A. McIntosh, F. Emmert-Streib, R. Kennedy, M. Salto-Tellez, K. M. Prise, D. G. McArt
Summary: RNA-seq technology poses challenges in the analysis of differential gene expression, but five models have been found to demonstrate robustness to sequencing alterations. The study indicates that the robustness of these models is dataset-agnostic and reliable for drawing conclusions when sample sizes are sufficiently large.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Genetics & Heredity
Matthew Alderdice, Stephanie G. Craig, Matthew P. Humphries, Alan Gilmore, Nicole Johnston, Victoria Bingham, Vicky Coyle, Seedevi Senevirathne, Daniel B. Longley, Maurice B. Loughrey, Stephen McQuaid, Jacqueline A. James, Manuel Salto-Tellez, Mark Lawler, Darragh G. McArt
Summary: The study identified IL2RB as a potential predictive biomarker for colorectal cancer patients receiving immune-checkpoint blockade therapy. IL2RB was found to be associated with immune-checkpoint genes and predominantly expressed in a subset of T-cells, showing a positive correlation with gene signatures of response to immune-checkpoint therapy.
NAR GENOMICS AND BIOINFORMATICS
(2021)
