Yan Dong PhD

Our lab studies the biology of advanced prostate cancer and mechanisms of therapeutic resistance.

A major focus of our recent research is on androgen receptor splice variants(AR-Vs) in castration-resistant prostate cancers. Work from my lab established the requirement of dimerization for AR-Vs to mediate resistance of prostate cancer to endocrine therapy, highlighting disrupting AR-V dimerization as a viable approach to inhibit AR-V signaling for prostate cancer treatment. We also revealed a clinically relevant mechanism of increased AR-V expression after endocrine therapy. We found that accumulation of AR-Vs is inevitable after endocrine therapy due to increased transcription of the AR gene, faster AR-FL protein decay, and efficient AR-V translation. This is vital to understanding the clinical significance of AR-Vs.

Another area of our research focus is on how intrachromosomal TMPRSS2-ERG gene fusion impacts prostate cancer disease progression. TMPRSS2-ERG gene fusion is one of the most frequent genetic alterations in prostate cancer. We found that the fusion perse may not be as important as the loss of the interstitial genes located between TMPRSS2 and ERG, such as FAM3B (Family With Sequence Similarity 3Member B), for prostate cancer disease progression.  We showed that FAM3Bworks as an intermediator of a self-governing AR feedback loop. Specifically, AR upregulates FAM3B expression by binding to an intronic enhancer to induce an enhancer-RNA and facilitate enhancer-promoter looping. FAM3B, in turn, attenuates AR signaling. Loss of FAM3B in prostate cancer causes an exit from this autoregulatory loop to unleash AR activity and prostate cancer progression. Our work demonstrates the functional significance of gene loss dueto intrachromosomal fusion events in cancer biology. This is a largely understudied area of investigation.

ORCID     identifier: 0000-0003-1622-5354

MyNCBI     Link: http://www.ncbi.nlm.nih.gov/sites/myncbi/yan.dong.2/bibliography/40318696/public/?sort=date&direction=ascending

Selected     Publications:

• Carlos M.     Roggero, Lianjin Jin, Subing Cao, Rajni Sonavane, Noa G Kopplin, Hui Ta,     Dede N Ekoue, Michael Witwer, Hong Liu, Tianfang Ma, Daniel Gioeli, Ganesh     V. Raj, Yan Dong. (2021) A detailed characterization of stepwise     activation of the androgen receptor variant 7 in prostate cancer cells. Oncogene,     40:1106–1117.
• Tianfang Ma,     Shanshan Bai, Yanfeng Qi, Yang Zhan, Nathan Ungerleider, Derek Y. Zhang,     Taavi Neklesa, Eva Corey, Scott M. Dehm, Kun Zhang, Erik K.     Flemington, and Yan Dong. (2021) Increased transcription and high     translation efficiency lead to accumulation of androgen receptor splice     variant after androgen deprivation therapy. Cancer Letters,     504:37-48.
• Subing Cao, Tianfang Ma, Nathan     Ungerleider, Claire Roberts, Margaret Kobelski, Lianjin Jin, Monica     Concha, Xia Wang, Melody Baddoo, Ladan Fazli, Holly M Nguyen, Eva Corey,     Elisa Ledet, Rubin Zhang, Jonathan L. Silberstein, Wensheng Zhang, Kun     Zhang, Oliver Sartor, Xuesen Dong, Erik K. Flemington, and Yan Dong.     (2019) Circular RNAs add diversity to androgen receptor isoform repertoire     in castration-resistant prostate cancer. Oncogene, 38:7060-7072.
• Shanshan Bai,     Subing Cao, Lianjin Jin, Margaret Kobelski, Blake Schouest, Xiaojie Wang,     Nathan Ungerleider, Melody Baddoo, Wensheng Zhang, Eva Corey, Robert     L. Vessella, Xuesen Dong, Kun Zhang, Xianghui Yu, Erik K. Flemington, and Yan     Dong. (2019) A Positive Role of c-Myc in Regulating Androgen Receptor     and its Splice Variants in Prostate Cancer. Oncogene, 38:4977–4989.    
• Y Zhan, G Zhang, X Wang, Y Qi,     S Bai, D Li, T Ma, O Sartor, EK Flemington, H Zhang, P Lee, and Y Dong.     (2017) Interplay between cytoplasmic and nuclear androgen receptor splice     variants mediate castration resistance. Molecular Cancer Research, 15, 59-68. Featured in the "Molecular     Cancer Research Highlights: Selected Articles from This Issue" with a     figure.
• D Xu, Y Zhan, Y Qi,     B Cao, S Bai, W Xu, SS Gambhir, P Lee, O Sartor, EK Flemington, H Zhang,     CD Hu, and Y Dong.  (2015) Androgen receptor splice variants     dimerize to transactivate target genes. Cancer Research, 75,     3663-3671.

Editorial: Emmanuel S. Antonarakis and Jun Luo. (2015) AR splicevariant dimerization - clinical implications Nature Reviews Urology, 12,431-433.

Topics (Keywords/Tags): prostate cancer, androgen receptor, therapy resistance, TMPRSS2-ERG translocation

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