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42 results on '"Zhang, Yajia"'

1. Optimal Vehicle Trajectory Planning for Static Obstacle Avoidance using Nonlinear Optimization

Author

Zhang, Yajia, Sun, Hongyi, Chai, Ruizhi, Kang, Daike, Li, Shan, and Li, Liyun

Subjects
Computer Science - Robotics
Abstract

Vehicle trajectory planning is a key component for an autonomous driving system. A practical system not only requires the component to compute a feasible trajectory, but also a comfortable one given certain comfort metrics. Nevertheless, computation efficiency is critical for the system to be deployed as a commercial product. In this paper, we present a novel trajectory planning algorithm based on nonlinear optimization. The algorithm computes a kinematically feasible and comfort-optimal trajectory that achieves collision avoidance with static obstacles. Furthermore, the algorithm is time efficient. It generates an 6-second trajectory within 10 milliseconds on an Intel i7 machine or 20 milliseconds on an Nvidia Drive Orin platform.

Published
2023

2. Interactive Trajectory Planner for Mandatory Lane Changing in Dense Non-Cooperative Traffic

Author

Liu, Xiangguo, Chen, Jianxing, Li, Shan, Zhang, Yajia, Yu, Hongtao, Huang, Fuqiang, Liu, Jiechao, Wang, Chao, Li, Liyun, and Zhu, Qi

Subjects
Computer Science - Robotics
Abstract

When the traffic stream is extremely congested and surrounding vehicles are not cooperative, the mandatory lane changing can be significantly difficult. In this work, we propose an interactive trajectory planner, which will firstly attempt to change lanes as long as safety is ensured. Based on receding horizon planning, the ego vehicle can abort or continue changing lanes according to surrounding vehicles' reactions. We demonstrate the performance of our planner in extensive simulations with eight surrounding vehicles, initial velocity ranging from 0.5 to 5 meters per second, and bumper to bumper gap ranging from 4 to 10 meters. The ego vehicle with our planner can change lanes safely and smoothly. The computation time of the planner at every step is within 10 milliseconds in most cases on a laptop with 1.8GHz Intel Core i7-10610U.

Published
2023

3. Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study.

Author

Sallman, David, Al Malki, Monzr, Asch, Adam, Wang, Eunice, Jurcic, Joseph, Bradley, Terrence, Flinn, Ian, Pollyea, Daniel, Kambhampati, Suman, Tanaka, Tiffany, Zeidner, Joshua, Garcia-Manero, Guillermo, Jeyakumar, Deepa, Komrokji, Rami, Lancet, Jeffrey, Kantarjian, Hagop, Gu, Lin, Zhang, Yajia, Tan, Anderson, Chao, Mark, OHear, Carol, Ramsingh, Giridharan, Lal, Indu, Vyas, Paresh, and Daver, Naval

Subjects
Humans, Azacitidine, Myelodysplastic Syndromes, Antibodies, Monoclonal, Humanized, Progression-Free Survival, Leukemia, Myeloid, Acute, Treatment Outcome
Abstract

PURPOSE: Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a dont-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479). PATIENTS AND METHODS: Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once-weekly or once-every-2-week maintenance dose. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and complete remission (CR) rate. RESULTS: Ninety-five patients were treated. Revised International Prognostic Scoring System risk was intermediate/high/very high in 27%, 52%, and 21%, respectively. Fifty-nine (62%) had poor-risk cytogenetics and 25 (26%) had TP53 mutation. The most common treatment-emergent adverse effects included constipation (68%), thrombocytopenia (55%), and anemia (52%). Median hemoglobin change from baseline to first postdose assessment was -0.7 g/dL (range, -3.1 to +2.4). CR rate and overall response rate were 33% and 75%, respectively. Median time to response, duration of CR, duration of overall response, and progression-free survival were 1.9, 11.1, 9.8, and 11.6 months, respectively. Median overall survival (OS) was not reached with 17.1-month follow-up. In TP53-mutant patients, 40% achieved CR with median OS of 16.3 months. Thirty-four patients (36%) had allogeneic stem-cell transplant with 77% 2-year OS. CONCLUSION: Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ClinicalTrials.gov identifier: NCT04313881 [ENHANCE]).

Published
2023

4. Optimal Trajectory Generation for Autonomous Vehicles Under Centripetal Acceleration Constraints for In-lane Driving Scenarios

Author

Zhang, Yajia, Sun, Hongyi, Zhou, Jinyun, Hu, Jiangtao, and Miao, Jinghao

Subjects
Computer Science - Robotics
Abstract

This paper presents a noval method that generates optimal trajectories for autonomous vehicles for in-lane driving scenarios. The method computes a trajectory using a two-phase optimization procedure. In the first phase, the optimization procedure generates a close-form driving guide line with differetiable curvatures. In the second phase, the procedure takes the driving guide line as input, and outputs dynamically feasible, jerk and time optimal trajectories for vehicles driving along the guide line. This method is especially useful for generating trajectories at curvy road where the vehicles need to apply frequent accelerations and decelerations to accommodate centripetal acceleration limits., Comment: IEEE International Conference on Intelligent Transportation Systems (ITSC) 2019

Published
2021
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5. Optimal Vehicle Path Planning Using Quadratic Optimization for Baidu Apollo Open Platform

Author

Zhang, Yajia, Sun, Hongyi, Zhou, Jinyun, Pan, Jiacheng, Hu, Jiangtao, and Miao, Jinghao

Subjects
Computer Science - Robotics
Abstract

Path planning is a key component in motion planning for autonomous vehicles. A path specifies the geometrical shape that the vehicle will travel, thus, it is critical to safe and comfortable vehicle motions. For urban driving scenarios, autonomous vehicles need the ability to navigate in cluttered environment, e.g., roads partially blocked by a number of vehicles/obstacles on the sides. How to generate a kinematically feasible and smooth path, that can avoid collision in complex environment, makes path planning a challenging problem. In this paper, we present a novel quadratic programming approach that generates optimal paths with resolution-complete collision avoidance capability., Comment: accepted by Intelligent Vehicle Symposium (IV) 2020

Published
2021
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6. Genomic alterations in DNA damage response (DDR) genes in HR+/HER2- metastatic breast cancer (mBC) and impact on clinical efficacy with sacituzumab govitecan (SG): Biomarker results from TROPICS-02 study.

Author

Bardia, Aditya, primary, Zhang, Yi, additional, Marmé, Frederik, additional, Schmid, Peter, additional, Cortes, Javier, additional, Tolaney, Sara M., additional, Zhang, Yajia, additional, Yoon, Oh Kyu, additional, Verret, Wendy, additional, Das Thakur, Meghna, additional, and Rugo, Hope S., additional

Published
2024
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7. Analysis of the androgen receptor–regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression

Author

Zhang, Yajia, Pitchiaya, Sethuramasundaram, Cieślik, Marcin, Niknafs, Yashar S, Tien, Jean C-Y, Hosono, Yasuyuki, Iyer, Matthew K, Yazdani, Sahr, Subramaniam, Shruthi, Shukla, Sudhanshu K, Jiang, Xia, Wang, Lisha, Liu, Tzu-Ying, Uhl, Michael, Gawronski, Alexander R, Qiao, Yuanyuan, Xiao, Lanbo, Dhanasekaran, Saravana M, Juckette, Kristin M, Kunju, Lakshmi P, Cao, Xuhong, Patel, Utsav, Batish, Mona, Shukla, Girish C, Paulsen, Michelle T, Ljungman, Mats, Jiang, Hui, Mehra, Rohit, Backofen, Rolf, Sahinalp, Cenk S, Freier, Susan M, Watt, Andrew T, Guo, Shuling, Wei, John T, Feng, Felix Y, Malik, Rohit, and Chinnaiyan, Arul M

Subjects
Biochemistry and Cell Biology, Biological Sciences, Cancer, Prostate Cancer, Genetics, Aging, Urologic Diseases, Aetiology, 2.1 Biological and endogenous factors, Androgens, Cell Line, Tumor, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Male, Prostate, Prostatic Neoplasms, RNA, Long Noncoding, Receptors, Androgen, Signal Transduction, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.

Published
2018

8. The lncRNA1‐miR6288b‐3p‐PpTCP4‐PpD2 module regulates peach branch number by affecting brassinosteroid biosynthesis.

Author

Wang, Xiaobei, Yan, Lixia, Li, Tianhao, Zhang, Jie, Zhang, Yajia, Zhang, Junjie, Lian, Xiaodong, Zhang, Haipeng, Zheng, Xianbo, Hou, Nan, Cheng, Jun, Wang, Wei, Zhang, Langlang, Ye, Xia, Li, Jidong, Feng, Jiancan, and Tan, Bin

Subjects
GENE expression, BIOSYNTHESIS, PEACH, FRUIT trees, GENETIC transcription, LINCRNA
Abstract

Summary: Branch number is one of the most important agronomic traits of fruit trees such as peach. Little is known about how LncRNA and/or miRNA modules regulate branching through transcription factors.Here, we used molecular and genetic tools to clarify the molecular mechanisms underlying brassinosteroid (BR) altering plant branching.We found that the number of sylleptic branch and BR content in pillar peach ('Zhaoshouhong') was lower than those of standard type ('Okubo'), and exogenous BR application could significantly promote branching. PpTCP4 expressed great differentially comparing 'Zhaoshouhong' with 'Okubo'. PpTCP4 could directly bind to DWARF2 (PpD2) and inhibited its expression. PpD2 was the only one differentially expressed key gene in the path of BR biosynthesis. At the same time, PpTCP4 was identified as a target of miR6288b‐3p. LncRNA1 could act as the endogenous target mimic of miR6288b‐3p and repress expression of miR6288b‐3p. Three deletions and five SNP sites of lncRNA1 promoter were found in 'Zhaoshouhong', which was an important cause of different mRNA level of PpTCP4 and BR content. Moreover, overexpressed PpTCP4 significantly inhibited branching.A novel mechanism in which the lncRNA1‐miR6288b‐3p‐PpTCP4‐PpD2 module regulates peach branching number was proposed. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy

Author

Li, Jing, Wang, Weichao, Zhang, Yajia, Cieslik, Marcin, Guo, Jipeng, Tan, Mengyao, Green, Michael D., Wang, Weimin, Lin, Heng, Li, Wei, Wei, Shuang, Zhou, Jiajia, Li, Gaopeng, Jing, Xiaojun, Vatan, Linda, Zhao, Lili, Bitler, Benjamin, Zhang, Rugang, Cho, Kathleen R., Dou, Yali, Kryczek, Ilona, Chan, Timothy A., Huntsman, David, Chinnaiyan, Arul M., and Zou, Weiping

Subjects
Cancer treatment -- Analysis, Epigenetic inheritance -- Genetic aspects -- Analysis, Cancer genetics -- Genetic aspects -- Development and progression, Cancer -- Genetic aspects -- Development and progression, Genes -- Analysis -- Genetic aspects, Chromatin -- Genetic aspects -- Analysis, Immunotherapy -- Analysis, Gene expression -- Analysis -- Genetic aspects, T cells -- Genetic aspects -- Analysis, Biochemistry, Cancer research, Tumors, Health care industry, University of Michigan. Medical School
Abstract

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy., Introduction Tumor-infiltrating T cells are positively associated with patient survival in many types of human cancer (1-3). Type I and type II IFN gene signatures correlate with clinical responses to [...]

Published
2020
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16. Data from Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer

Author

Xiao, Lanbo, primary, Tien, Jean C., primary, Vo, Josh, primary, Tan, Mengyao, primary, Parolia, Abhijit, primary, Zhang, Yajia, primary, Wang, Lisha, primary, Qiao, Yuanyuan, primary, Shukla, Sudhanshu, primary, Wang, Xiaoju, primary, Zheng, Heng, primary, Su, Fengyun, primary, Jing, Xiaojun, primary, Luo, Esther, primary, Delekta, Andrew, primary, Juckette, Kristin M., primary, Xu, Alice, primary, Cao, Xuhong, primary, Alva, Ajjai S., primary, Kim, Youngsoo, primary, MacLeod, A. Robert, primary, and Chinnaiyan, Arul M., primary

Published
2023
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17. Supplementary Figures from Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer

Author

Xiao, Lanbo, primary, Tien, Jean C., primary, Vo, Josh, primary, Tan, Mengyao, primary, Parolia, Abhijit, primary, Zhang, Yajia, primary, Wang, Lisha, primary, Qiao, Yuanyuan, primary, Shukla, Sudhanshu, primary, Wang, Xiaoju, primary, Zheng, Heng, primary, Su, Fengyun, primary, Jing, Xiaojun, primary, Luo, Esther, primary, Delekta, Andrew, primary, Juckette, Kristin M., primary, Xu, Alice, primary, Cao, Xuhong, primary, Alva, Ajjai S., primary, Kim, Youngsoo, primary, MacLeod, A. Robert, primary, and Chinnaiyan, Arul M., primary

Published
2023
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18. Supplementary Methods and References from Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

Author

McDaniel, Andrew S., primary, Hovelson, Daniel H., primary, Cani, Andi K., primary, Liu, Chia-Jen, primary, Zhai, Yali, primary, Zhang, Yajia, primary, Weizer, Alon Z., primary, Mehra, Rohit, primary, Feng, Felix Y., primary, Alva, Ajjai S., primary, Morgan, Todd M., primary, Montgomery, Jeffrey S., primary, Siddiqui, Javed, primary, Sadis, Seth, primary, Bandla, Santhoshi, primary, Williams, Paul D., primary, Cho, Kathleen R., primary, Rhodes, Daniel R., primary, and Tomlins, Scott A., primary

Published
2023
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19. Data from Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

Author

McDaniel, Andrew S., primary, Hovelson, Daniel H., primary, Cani, Andi K., primary, Liu, Chia-Jen, primary, Zhai, Yali, primary, Zhang, Yajia, primary, Weizer, Alon Z., primary, Mehra, Rohit, primary, Feng, Felix Y., primary, Alva, Ajjai S., primary, Morgan, Todd M., primary, Montgomery, Jeffrey S., primary, Siddiqui, Javed, primary, Sadis, Seth, primary, Bandla, Santhoshi, primary, Williams, Paul D., primary, Cho, Kathleen R., primary, Rhodes, Daniel R., primary, and Tomlins, Scott A., primary

Published
2023
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20. Supplementary Figures S1-S5 from Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

Author

McDaniel, Andrew S., primary, Hovelson, Daniel H., primary, Cani, Andi K., primary, Liu, Chia-Jen, primary, Zhai, Yali, primary, Zhang, Yajia, primary, Weizer, Alon Z., primary, Mehra, Rohit, primary, Feng, Felix Y., primary, Alva, Ajjai S., primary, Morgan, Todd M., primary, Montgomery, Jeffrey S., primary, Siddiqui, Javed, primary, Sadis, Seth, primary, Bandla, Santhoshi, primary, Williams, Paul D., primary, Cho, Kathleen R., primary, Rhodes, Daniel R., primary, and Tomlins, Scott A., primary

Published
2023
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21. Supplementary Figure Legends from Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

Author

McDaniel, Andrew S., primary, Hovelson, Daniel H., primary, Cani, Andi K., primary, Liu, Chia-Jen, primary, Zhai, Yali, primary, Zhang, Yajia, primary, Weizer, Alon Z., primary, Mehra, Rohit, primary, Feng, Felix Y., primary, Alva, Ajjai S., primary, Morgan, Todd M., primary, Montgomery, Jeffrey S., primary, Siddiqui, Javed, primary, Sadis, Seth, primary, Bandla, Santhoshi, primary, Williams, Paul D., primary, Cho, Kathleen R., primary, Rhodes, Daniel R., primary, and Tomlins, Scott A., primary

Published
2023
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22. Supplementary Tables S1-S4 from Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

Author

McDaniel, Andrew S., primary, Hovelson, Daniel H., primary, Cani, Andi K., primary, Liu, Chia-Jen, primary, Zhai, Yali, primary, Zhang, Yajia, primary, Weizer, Alon Z., primary, Mehra, Rohit, primary, Feng, Felix Y., primary, Alva, Ajjai S., primary, Morgan, Todd M., primary, Montgomery, Jeffrey S., primary, Siddiqui, Javed, primary, Sadis, Seth, primary, Bandla, Santhoshi, primary, Williams, Paul D., primary, Cho, Kathleen R., primary, Rhodes, Daniel R., primary, and Tomlins, Scott A., primary

Published
2023
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28. The Landscape of Circular RNA in Cancer

Author

Vo, Josh N., primary, Cieslik, Marcin, additional, Zhang, Yajia, additional, Shukla, Sudhanshu, additional, Xiao, Lanbo, additional, Zhang, Yuping, additional, Wu, Yi-Mi, additional, Dhanasekaran, Saravana M., additional, Engelke, Carl G., additional, Cao, Xuhong, additional, Robinson, Dan R., additional, Nesvizhskii, Alexey I., additional, and Chinnaiyan, Arul M., additional

Published
2019
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29. Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer

Author

Xiao, Lanbo, primary, Tien, Jean C., additional, Vo, Josh, additional, Tan, Mengyao, additional, Parolia, Abhijit, additional, Zhang, Yajia, additional, Wang, Lisha, additional, Qiao, Yuanyuan, additional, Shukla, Sudhanshu, additional, Wang, Xiaoju, additional, Zheng, Heng, additional, Su, Fengyun, additional, Jing, Xiaojun, additional, Luo, Esther, additional, Delekta, Andrew, additional, Juckette, Kristin M., additional, Xu, Alice, additional, Cao, Xuhong, additional, Alva, Ajjai S., additional, Kim, Youngsoo, additional, MacLeod, A. Robert, additional, and Chinnaiyan, Arul M., additional

Published
2018
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30. Abstract 3288: The landscape of circular RNA in cancer

Author

Vo, Josh N., primary, Zhang, Yajia, additional, Shukla, Sudhanshu, additional, Xiao, Lanbo, additional, Robinson, Dan, additional, Wu, Yi-Mi, additional, Gao, Sisi, additional, Engelke, Carl, additional, Cao, Xuhong, additional, Nesvizhskii, Alexey, additional, and Chinnaiyan, Arul, additional

Published
2018
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31. Abstract 2458: The androgen receptor-regulated lncRNA landscape reveals a role forARlnc1in prostate cancer progression

Author

Zhang, Yajia, primary, Pitchiaya, Sethuramasundaram, additional, Cieślik, Marcin, additional, Niknafs, Yashar S., additional, Tien, Jean C., additional, Hosono, Yasuyuki, additional, Wang, Lisha, additional, Qiao, Yuanyuan, additional, Cao, Xuhong, additional, Ljungman, Mats, additional, Jiang, Hui, additional, Mehra, Rohit, additional, Guo, Shuling, additional, Malik, Rohit, additional, and Chinnaiyan, Arul M., additional

Published
2018
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36. Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

Author

McDaniel, Andrew S., primary, Hovelson, Daniel H., additional, Cani, Andi K., additional, Liu, Chia-Jen, additional, Zhai, Yali, additional, Zhang, Yajia, additional, Weizer, Alon Z., additional, Mehra, Rohit, additional, Feng, Felix Y., additional, Alva, Ajjai S., additional, Morgan, Todd M., additional, Montgomery, Jeffrey S., additional, Siddiqui, Javed, additional, Sadis, Seth, additional, Bandla, Santhoshi, additional, Williams, Paul D., additional, Cho, Kathleen R., additional, Rhodes, Daniel R., additional, and Tomlins, Scott A., additional

Published
2015
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42. Discovery and Characterization of Non-Coding RNAs with Therapeutic and Diagnostic Potential in Prostate Cancer

Author

Zhang, Yajia

Subjects
non-coding RNA, prostate cancer
Abstract

Prostate cancer is the most common malignancy and the second leading cause of death in American men. Primary prostate cancer is often hormone-dependent and relies on signaling through the androgen receptor (AR); therefore, the majority of patients are responsive to front-line treatment with androgen-deprivation therapy. However, some cases progress to an incurable stage of the disease known as castration-resistant prostate cancer (CRPC), which still relies on AR signaling. Substantial efforts have been undertaken to study sustained AR signaling in CRPC. The mechanisms identified include AR amplifications, AR splice variants, alterations in cofactor recruitment, and ligand-independent activation via crosstalk with signal transduction pathways. However, few studies have investigated the roles of non-coding RNAs (ncRNAs) in AR signaling axis. Noncoding RNAs are a class of transcripts with diverse and largely uncharacterized biological functions. Through crosstalk with chromatin, DNA, RNA, and proteins, ncRNAs function via chromatin remodeling as well as transcriptional and post-transcriptional regulation. To discover long non-coding RNAs (lncRNAs) with therapeutic or diagnostic potential in prostate cancer, we have performed a comprehensive RNA-seq profile investigation of cancer-associated, AR-regulated lncRNAs from prostate cancer cell lines and patient tissue samples. Through this analysis, we identified ARLNC1 (AR-regulated long noncoding RNA 1), an important lncRNA that is significantly enriched in prostate lineage and associates with prostate cancer progression. ARLNC1 is directly induced by the AR protein and modulates AR signaling. ARLNC1 knockdown suppresses AR expression, AR-responsive genes, and prostate cancer growth in vitro and in vivo. Further dissection of ARLNC1 cellular mechanism showed that the lncRNA stabilized the AR transcript via RNA-RNA interaction. This positive feedback loop, where AR transcriptionally regulates ARLNC1 and ARLNC1 regulates its master regulator (AR) post-transcriptionally, suggests that lncRNAs can serve as novel regulatory nodes on AR signaling pathway. Because modulation of ARLNC1 expression levels resulted in a striking proliferation phenotype, it is hypothesized that ARLNC1 inhibition could be used therapeutically for the treatment of prostate cancer. Supporting this hypothesis, antisense oligonucleotides (ASOs) targeting ARLNC1 inhibited prostate cancer cell growth in vitro and in vivo. The fact that ARLNC1 acts upstream of AR signaling presents the possibility that targeting ARLNC1 may afford an additional option to patients that have de novo or acquired resistance to therapies targeting AR itself. In addition, we evaluated the clinical relevance of ARLNC1 as a diagnostic biomarker. Among the prostate samples, ARLNC1 expression was significantly higher in localized and metastatic prostate cancers than in benign tissues, as assessed by RNA-seq and RNA in situ hybridization. Moreover, there exists an association of ARLNC1 levels with accentuated AR signaling and luminal epithelial differentiation in patient tumors, both of which are important clinical considerations for anti-androgen treatment. Finally, we characterized expression patterns of another type of non-coding RNA, circular RNA (circRNA). A set of circRNAs were identified as candidate biomarkers for prostate cancer. They have higher stability compared to linear transcripts. We further validated the existence of a novel class of circular transcripts, termed read-through circRNAs, that involve exons originating from different genes. Additionally, circRNAs can be detected in patient urine samples and may be developed into non-invasive biomarkers. Taken together, this work defines essential roles for ARLNC1 in prostate cancer progression, uncovers novel aspects of AR signaling and lncRNA biology, and underscores the clinical potential of non-coding RNAs as diagnostic markers or therapeutic targets in prostate cancer.

Published
2019

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