Article
Biochemistry & Molecular Biology
Lijuan Yin, Jingjing Li, Jing Wang, Tianjie Pu, Jing Wei, Qinlong Li, Boyang Jason Wu
Summary: Perineural invasion (PNI) is an important indicator of cancer progression and poor prognosis, especially in prostate cancer. The study revealed that MAOA plays a crucial role in promoting PNI in PC, and inhibition of MAOA can reduce PNI and potentially serve as a targeted treatment strategy for PC in the future.
Article
Cell Biology
Zhenfeng Shi, Chutian Xiao, Tengceng Li, Jieying Wu, Ke Li
Summary: The study suggests that high expression of BZW1 in prostate cancer is associated with tumor progression and poor prognosis, promoting cell proliferation by regulating the TGF-beta 1/Smad pathway.
Article
Medicine, Research & Experimental
Wenjie Lai, Weian Zhu, Xiaojuan Li, Yuefu Han, Yu Wang, Qu Leng, Mingzhao Li, Xingqiao Wen
Summary: This study demonstrates that GTSE1 is significantly upregulated in prostate cancer and negatively correlates with patient prognosis. GTSE1 promotes prostate cancer cell proliferation through the SP1/FOXM1 signaling pathway, suggesting its potential as a prognostic marker and therapeutic target in prostate cancer.
LABORATORY INVESTIGATION
(2021)
Article
Oncology
Klaudia Stempa, Dominika Wokolorczyk, Wojciech Kluzniak, Emilia Rogoza-Janiszewska, Karolina Malinska, Helena Rudnicka, Tomasz Huzarski, Jacek Gronwald, Katarzyna Gliniewicz, Tadeusz Debniak, Anna Jakubowska, Marcin Lener, Joanna Tomiczek-Szwiec, Pawel Domagala, Malwina Suszynska, Piotr Kozlowski, Tomasz Kluz, Mariusz Naczk, Jan Lubinski, Steven A. Narod, Mohammad R. Akbari, Cezary Cybulski
Summary: The study found that mutations in the BARD1 gene do not increase the risk of prostate cancer or influence its characteristics or survival. However, BARD1 is a breast cancer predisposition gene, and female relatives of men with BARD1 mutations may benefit from this information.
Article
Biochemistry & Molecular Biology
Jing Wang, Jingjing Li, Lijuan Yin, Tianjie Pu, Jing Wei, Varsha Karthikeyan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: This study reveals that neuropilin 2 (NRP2) is upregulated in NEPC and plays a role in driving NEPC development and resistance. NRP2 interacts with AR to suppress AR signaling, and activates STAT3 phosphorylation by interacting with VEGFR2, promoting NEPC differentiation and growth.
Article
Oncology
Yiming Su, Yu Zhang, Jing Zhao, Wenhao Zhou, Wenhao Wang, Bangmin Han, Xiaohai Wang
Summary: The study showed that FOXA1 promotes endothelial cell proliferation, migration, and tube formation in prostate cancer cells. Mechanistically, FOXA1 increases the production of pro-angiogenic factors such as EGF, Endothelin-1, and Endoglin. In vivo and clinical samples investigations further confirmed the role of FOXA1 in enhancing prostate cancer angiogenesis.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Yafei Li, Jing Tang, Jing Li, Yaru Du, Fuqiang Bai, Lirui Yang, Xiaobo Li, Xiaoming Jin, Tianzhen Wang
Summary: This study identified that ARID3A enhances chemosensitivity of colon cancer cells by inhibiting AKR1C3, which leads to better prognosis for patients.
CELL BIOLOGY INTERNATIONAL
(2022)
Article
Medicine, Research & Experimental
Tao Shen, Wei Wang, Wolong Zhou, Ilsa Coleman, Qinbo Cai, Bingning Dong, Michael M. Ittmann, Chad J. Creighton, Yingnan Bian, Yanling Meng, David R. Rowley, Peter S. Nelson, David D. Moore, Feng Yang
Summary: The study revealed that MAPK4 promotes prostate cancer growth and castration resistance by activating GATA2/AR and AKT pathways. Activation of both GATA2/AR and AKT is necessary for MAPK4 tumor-promoting activity.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Shih-Bo Huang, D. Thapa, A. R. Munoz, S. S. Hussain, X. Yang, R. G. Bedolla, P. Osmulski, M. E. Gaczynska, Z. Lai, Yu-Chiao Chiu, Li-Ju Wang, Y. Chen, P. Rivas, C. Shudde, R. L. Reddick, H. Miyamoto, R. Ghosh, A. P. Kumar
Summary: SIRT1 plays a contextual role in prostate cancer, affecting tumor growth, hormone sensitivity, and gene signatures. Lowering SIRT1 levels may potentially provide new avenues to effectively prevent prostate cancer recurrence.
Article
Oncology
Daniela Carreno, Nestor B. Corro, Javier F. Cerda-Infante, Carolina E. Echeverria, Catalina A. Asencio-Barria, Veronica A. Torres-Estay, Gonzalo A. Mayorga-Weber, Pablo A. Rojas, Loreto P. Veliz, Pedro A. Cisternas, Viviana P. Montecinos, Ignacio F. San Francisco, Manuel A. Varas-Godoy, Paula C. Sotomayor, Maite A. Castro, Francisco J. Nualart, Nibaldo C. Inestrosa, Alejandro S. Godoy
Summary: Prostate cancer cells overexpress fructose transporters compared with benign cells, and fructose can stimulate proliferation and invasion of prostate cancer cells. This study suggests that fructose may serve as an alternative energy source for prostate cancer cells, promoting their growth and aggressiveness both in vitro and in vivo.
Article
Gastroenterology & Hepatology
Xiaoting Sun, Xingkang He, Yin Zhang, Kayoko Hosaka, Patrik Andersson, Jing Wu, Jieyu Wu, Xu Jing, Qiqiao Du, Xiaoli Hui, Bo Ding, Ziheng Guo, An Hong, Xuan Liu, Yan Wang, Qing Ji, Rudi Beyaert, Yunlong Yang, Qi Li, Yihai Cao
Summary: The study found that IL-33 and CXCL3 are elevated in PDAC patients, correlated with tumor inflammation and poor survival rates. The IL-33-ST2-MYC pathway regulates the high production of CXCL3. Activation of CXCR2 by CXCL3 induces a CAF-to-myoCAF transition, promoting PDAC metastasis.
Article
Biochemistry & Molecular Biology
Ashutosh S. Yende, Emily C. Williams, Andrew Pletcher, Alexandra Helfand, Helen Ibeawuchi, Tanya M. North, Patricia S. Latham, Anelia Horvath, Maho Shibata
Summary: TRIM28 is found to be significantly upregulated in high-grade and metastatic prostate cancers. Through a genetically-engineered mouse model, scientists discovered that TRIM28 plays an important role in the progression of prostate cancer. Despite a reduction in luminal cells resembling proximal luminal lineage cells, the mouse prostates still evolved into invasive prostate carcinoma with a shorter overall survival.
Article
Multidisciplinary Sciences
Daisuke Obinata, Daigo Funakoshi, Kenichi Takayama, Makoto Hara, Birunthi Niranjan, Linda Teng, Mitchell G. Lawrence, Renea A. Taylor, Gail P. Risbridger, Yutaka Suzuki, Satoru Takahashi, Satoshi Inoue
Summary: The study investigated treatment methods for AR-negative PC and identified the role of neural genes in tumor development through the discovery and research of OCT1-target genes. Knockdown of STNB1 and PFN2 genes showed inhibitory effects on tumor growth, highlighting their potential as therapeutic targets for AR-negative PC.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Sambad Sharma, Xinhong Pei, Fei Xing, Shih-Ying Wu, Kerui Wu, Abhishek Tyagi, Dan Zhao, Ravindra Deshpande, Marco Gabriel Ruiz, Ravi Singh, Feng Lyu, Kounosuke Watabe
Summary: The study identified Regucalcin (RGN) as a gene that promotes dormancy in prostate cancer and patients with higher RGN expression levels have better recurrence-free and overall survival. RGN promotes tumor dormancy by regulating p38 MAPK, Erk signaling, and FOXM1 expression, while also suppressing angiogenesis through increased secretory miR-23c levels in exosomes. Additionally, RGN downstream target genes independently predict longer recurrence-free survival in patients, suggesting RGN signaling and exosomal miR-23c as potential biomarkers for predicting recurrence.
Article
Oncology
Shiyu Wang, Fan Chao, Cong Zhang, Dunsheng Han, Guoxiong Xu, Gang Chen
Summary: The study found that circPFKP was significantly increased in prostate cancer tissues compared to noncancerous tissues, and was correlated with PCa risk classification, N stage, and prognostic group. CircPFKP promotes PCa cell proliferation by interacting with IMPDH2, and its production may be facilitated by hnRNPF binding.
Article
Biochemical Research Methods
Spiro C. Stilianoudakis, Maggie A. Marshall, Mikhail G. Dozmorov
Summary: The preciseTAD framework, trained on high-resolution genome annotation data, accurately predicts 3D domain boundaries at base-pair resolution, providing a new tool for better understanding how genomic regulators shape the 3D structure of the genome.
Review
Oncology
Nuria Camina, Trevor M. Penning
Summary: The activation of the NRF2 transcription factor plays a crucial role in detoxifying electrophilic carcinogens and preventing cancer, yet can also potentially exacerbate carcinogenesis in certain contexts. Understanding the activation of the NRF2-KEAP1 signaling pathway, its epigenetic regulation, and its role in oncogenesis is essential for elucidating the mechanisms of cancer development.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
James D. Hampton, Erica J. Peterson, Samantha J. Katner, Tia H. Turner, Mohammad A. Alzubi, J. Chuck Harrell, Mikhail G. Dozmorov, Joseph B. McGee Turner, Pam J. Gigliotti, Vita Kraskauskiene, Mayuri Shende, Michael O. Idowu, Madhavi Puchalapalli, Bin Hu, Larisa Litovchick, Eriko Katsuta, Kazuaki Takabe, Nicholas P. Farrell, Jennifer E. Koblinski
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer without targetable biomarkers. This study found that sGAG levels can predict the sensitivity of TNBC to Triplatin, a platinum agent. Triplatin showed significant antitumor efficacy in TNBC models with high levels of sGAGs, even in carboplatin-resistant tumors. Improved neoadjuvant and adjuvant treatments may enhance the clinical outcome of TNBC.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Endocrinology & Metabolism
Ryan D. Paulukinas, Clementina A. Mesaros, Trevor M. Penning
Summary: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, characterized by hyperandrogenism. Research suggests that Aldo-keto reductase family 1 member C3 (AKR1C3) plays a significant role in the conversion of androgens in adipocytes, contributing to the hyperandrogenic profile of PCOS. This finding highlights AKR1C3 as a potential therapeutic target for mitigating the symptoms of PCOS, particularly through the modulation of 11-oxygenated androgens formed in adipocytes.
Article
Chemistry, Medicinal
Joseph D. Romano, Yun Hao, Jason H. Moore, Trevor M. Penning
Summary: ComptoxAI is a new data infrastructure that utilizes computational and artificial intelligence research to predict toxicology. It features a graph structured knowledge base that can quickly answer complex questions and includes various real-world use cases.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Garrison Komaniecki, Maria Del Carmen Camarena, Eric Gelsleichter, Rachel Mendoza, Mark Subler, Jolene J. Windle, Mikhail G. Dozmorov, Zhao Lai, Devanand Sarkar, Hening Lin
Summary: Nonalcoholic fatty liver disease is a major risk factor for hepatocellular carcinoma and involves lipid accumulation, inflammation, and tumorigenesis. This study discovered that AEG-1 is palmitoylated at residue cysteine 75 (Cys75) and that mutation of Cys75 to serine (Ser) abolishes this palmitoylation. Further experiments in mice revealed that the Cys75 mutation activates signaling pathways related to cell proliferation, motility, inflammation, angiogenesis, and lipid accumulation in hepatocytes. This finding suggests that palmitoylation restricts the oncogenic and NASH-promoting functions of AEG-1.
Article
Oncology
Cynthia Weigel, Melissa A. Maczis, Elisa N. D. Palladino, Christopher D. Green, Michael Maceyka, Chunqing Guo, Xiang-Yang Wang, Mikhail G. Dozmorov, Sheldon Milstien, Sarah Spiegel
Summary: This study reveals that inhibiting or deleting SphK2 can suppress breast tumor growth and metastasis by altering the tumor microenvironment. SphK2 deficiency leads to ceramide accumulation in stromal fibroblasts, which suppresses the activation of cancer-associated fibroblasts and restricts tumor formation. These findings highlight the novel role of SphK2 in regulating non-cell-autonomous functions in the tumor microenvironment.
Article
Chemistry, Medicinal
Anthony L. Su, Trevor M. Penning
Summary: 1-Nitropyrene (1-NP), a constituent of diesel exhaust, is a group 2A probable human carcinogen that can cause cancer through the covalent binding of electrophiles generated during nitroreduction to DNA. We discovered that aldo-keto reductases (AKRs) 1C1-1C3 and nuclear factor erythroid 2-related factor 2 (NRF2) play a significant role in the nitroreduction of 1-NP. Pharmacological and genetic experiments revealed that inhibiting AKR1C1 and AKR1C2 decreased nitroreduction, while activating NRF2 increased nitroreduction in certain cell lines. Moreover, NRF2 expression levels influenced the amount of 1-aminopyrene (1-AP) production, indicating the importance of NRF2 in 1-NP metabolic activation.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Andrea J. Detlefsen, Ryan D. Paulukinas, Trevor M. Penning
Summary: Steroid hormone-transforming enzymes play a crucial role in regulating the functions of steroid hormones. Mutations in these enzymes can cause endocrine disorders and have significant impacts on sexual development and other severe disorders. This review focuses on disease-associated germline coding mutations in the aldo-keto reductase (AKR) superfamily, uncovering the effects of these mutations on androgen metabolism, bile acid deficiency, and other diseases. However, further research is needed to fully understand the relationship between AKR mutations and diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
David C. Boyd, Emily K. Zboril, Amy L. Olex, Tess J. Leftwich, Nicole S. Hairr, Holly A. Byers, Aaron D. Valentine, Julia E. Altman, Mohammad A. Alzubi, Jacqueline M. Grible, Scott A. Turner, Andrea Ferreira-Gonzalez, Mikhail G. Dozmorov, J. Chuck Harrell
Summary: Basal-like breast cancers, which are the majority of triple-negative breast cancers, have high levels of PI3K pathway activity and are difficult to treat. PI3K inhibitors as single agents have limited efficacy in TNBC patients. This study aimed to identify drug combinations that can effectively inhibit tumor growth when used in conjunction with PI3K inhibitors.
Article
Chemistry, Medicinal
Krishnaiah Maddeboina, Sravan K. Jonnalagadda, Ahmed Morsy, Ling Duan, Yashpal S. Chhonker, Daryl J. Murry, Trevor M. Penning, Paul C. Trippier
Summary: AKR1C3 is overexpressed in castration-resistant prostate cancer and drives proliferation and aggressiveness by producing androgens. The study reports the optimization of AKR1C3 inhibitors and the discovery of a potent inhibitor, 5r, with high selectivity for AKR1C3. A prodrug strategy was used to improve pharmacokinetics, and the prodrug 4r was converted to the active form, 5r. In vivo experiments showed increased exposure and concentration of 5r compared to direct administration of the free acid. The prodrug 4r effectively reduced tumor volume without toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Saranya Chidambaranathan Reghupaty, Sadia Kanwal, Rachel G. Mendoza, Eva Davis, Haiwen Li, Zhao Lai, Mikhail G. Dozmorov, Milton Omar Faison, Rafat Ali Siddiqui, Devanand Sarkar
Summary: Hepatocellular carcinoma (HCC) is a common primary liver cancer influenced by chronic liver inflammation and race/ethnicity. Analysis of RNA-sequencing data revealed the activation of an inflammatory pathway in HCC tumors of African-American/Black patients. Ginger extract (GE), known for its anti-inflammatory properties, showed potential efficacy in inhibiting HCC cell growth, particularly in cells from African-American/Black patients. These findings suggest that a holistic diet containing ginger may benefit African-American/Black HCC patients.
Article
Biochemical Research Methods
Jonathan D. Ogata, Wancen Mu, Eric S. Davis, Bingjie Xue, J. Chuck Harrell, Nathan C. Sheffield, Douglas H. Phanstiel, Michael Love, Mikhail G. Dozmorov
Summary: Exclusion regions are abnormal sections of reference genomes where short sequencing reads pile up. Removing reads overlapping these regions improves biological signal, particularly in differential analysis. Multiple exclusion region sets have been created by labs, primarily available through ENCODE and Github, causing uncertainty in which sets to use. Additionally, gap regions like centromeres, telomeres, and short arms pose further considerations when generating exclusion sets.
Letter
Endocrinology & Metabolism
Trevor M. Penning, Andrea J. Detlefsen
Article
Endocrinology & Metabolism
Ryan D. Paulukinas, Trevor M. Penning
Summary: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, characterized by insulin resistance and hyperandrogenism. The study found that AKR1C3, induced by insulin, plays a role in promoting lipid overload through the induction of FASN in PCOS adipocytes. It was also discovered that AKR1C3 stabilizes AR and interacts with it, leading to the formation of lipid droplets. These findings suggest that AKR1C3 could be a therapeutic target for bifunctional inhibitors to reduce cardiometabolic disease in PCOS.