Journal
CANCER RESEARCH
Volume 81, Issue 16, Pages 4174-4182Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-20-4010
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Funding
- Department of Atomic Energy [RSI 4002]
- Science & Engineering Research Board (SERB), Department of Science Technology [CRG/2018/000985, EMR/2016/006233]
- SwarnaJayanti Fellowship, Department of Science and Technology [DST/SJF/LSA-02/2017-18]
- Department of Biotechnology [BT/PR28920/MED/122/176/2018]
- Department of Biotechnology, Govt. of India [BT/HRD-NBANWB/38/2019-20]
- Cancer Prevention and Research Institute of Texas (CPRIT) [RR170020]
- Science & Engineering Research Board (SERB), Department of Science & Technology (DST), Govt. of India [EMR/2016/006233]
- Council of Scientific and Industrial Research (CSIR), Govt. of India
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Despite progress in anticancer therapies, therapy resistance remains a challenge due to genetic and epigenetic heterogeneity in tumors. Enhancer elements and their transcribed noncoding RNAs, known as enhancer RNAs, play important roles in promoting oncogenesis and may serve as potential therapeutic targets or biomarkers in various cancer types.
Despite extensive progress in developing anticancer therapies, therapy resistance remains a major challenge that promotes disease relapse. The changes that lead to therapy resistance can be intrinsically present or may be initiated during treatment. Genetic and epigenetic heterogeneity in tumors make it more challenging to deal with therapy resistance. Recent advances in genome-wide analyses have revealed that the deregulation of distal gene regulatory elements, such as enhancers, appears in several pathophysiological conditions, including cancer. Beyond the conventional function of enhancers in recruiting transcription factors to gene promoters, enhancer elements are also transcribed into noncoding RNAs known as enhancer RNAs (eRNA). Accumulating evidence suggests that uncontrolled enhancer activity with aberrant eRNA expression promotes oncogenesis. Interestingly, tissue-specific, transcribed eRNAs from active enhancers can serve as potential therapeutic targets or biomarkers in several cancer types. This review provides a comprehensive overview of the mechanisms of enhancer transcription and eRNAs as well as their potential roles in cancer and drug resistance.
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