Coordinated AR and microRNA regulation in prostate cancer

Eringyte, Ieva; Losada, Joanna N. Zamarbide; Powell, Susan; Bevan, Charlotte L.; Fletcher, Claire

doi:10.1016/j.ajur.2020.06.003

Cited by 15 publications

(8 citation statements)

References 177 publications

(334 reference statements)

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“…Several variants, mutations, or even genomic rearrangements (TMPRSS2-ERG fusion is the most common in human prostate cancer, but is absent in small cell carcinoma of the bladder) are involved in pathophysiological situations correlated with AR signaling pathways; the complex interaction of each protein in a specific context may lead to different results, and represents a new pharmacological target for these pathologies, including bladder cancer [29]. New strategies that modulate AR signaling are developing, as demonstrated in the studies with long noncoding RNAs (lncRNAs), microRNAs, enhancer RNAs (eRNAs), and others [30][31][32][33]. The AR interacts with enzymes (cofactors) involved in the regulation of histone methylation, such as lysine-specific demethylase 1 (LSD1), KDM4B, KDM5B, KDM7A, EZH2, SMYD3 and PRMT5.…”

Section: Activation Of Androgen Receptor and Cofactorsmentioning

confidence: 99%

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

et al. 2021

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Bladder cancer (urothelial carcinoma) is one of the most frequently diagnosed neoplasms, with an estimated half a million new cases and 200,000 deaths per year worldwide. This pathology mainly affects men. Men have a higher risk (4:1) of developing bladder cancer than women. Cigarette smoking and exposure to chemicals such as aromatic amines, and aniline dyes have been established as risk factors for bladder cancer and may contribute to the sex disparity. Male internal genitalia, including the urothelium and prostate, are derived from urothelial sinus endoderm; both tissues express the androgen receptor (AR). Several investigations have shown evidence that the AR plays an important role in the initiation and development of different types of cancer including bladder cancer. In this article, we summarize the available data that help to explain the role of the AR in the development and progression of bladder cancer, as well as the therapies used for its treatment.

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Section: Activation Of Androgen Receptor and Cofactorsmentioning

confidence: 99%

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

et al. 2021

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“…These results indicate that miRNA-34a could be further targeted for drug resistance therapeutic purposes in hormone-resistant prostate cancer. In prostate cancer, miRNAs are reported to be modulators of androgen deprivation therapy (ADT) resistance [ 109 ]. Sun et al, (2012) [ 110 ] have reported that miRNA-221/222 are upregulated while miRNA-23b and miRNA-27b are downregulated in about 90% of metastatic castrate-resistant prostate cancer (mCRPC) cases compared with primary tumors.…”

Section: Mirna and Alternative Splicing-induced Drug Resistancementioning

confidence: 99%

MicroRNA and Alternative mRNA Splicing Events in Cancer Drug Response/Resistance: Potent Therapeutic Targets

et al. 2021

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Cancer is a multifaceted disease that involves several molecular mechanisms including changes in gene expression. Two important processes altered in cancer that lead to changes in gene expression include altered microRNA (miRNA) expression and aberrant splicing events. MiRNAs are short non-coding RNAs that play a central role in regulating RNA silencing and gene expression. Alternative splicing increases the diversity of the proteome by producing several different spliced mRNAs from a single gene for translation. MiRNA expression and alternative splicing events are rigorously regulated processes. Dysregulation of miRNA and splicing events promote carcinogenesis and drug resistance in cancers including breast, cervical, prostate, colorectal, ovarian and leukemia. Alternative splicing may change the target mRNA 3′UTR binding site. This alteration can affect the produced protein and may ultimately affect the drug affinity of target proteins, eventually leading to drug resistance. Drug resistance can be caused by intrinsic and extrinsic factors. The interplay between miRNA and alternative splicing is largely due to splicing resulting in altered 3′UTR targeted binding of miRNAs. This can result in the altered targeting of these isoforms and altered drug targets and drug resistance. Furthermore, the increasing prevalence of cancer drug resistance poses a substantial challenge in the management of the disease. Henceforth, molecular alterations have become highly attractive drug targets to reverse the aberrant effects of miRNAs and splicing events that promote malignancy and drug resistance. While the miRNA–mRNA splicing interplay in cancer drug resistance remains largely to be elucidated, this review focuses on miRNA and alternative mRNA splicing (AS) events in breast, cervical, prostate, colorectal and ovarian cancer, as well as leukemia, and the role these events play in drug resistance. MiRNA induced cancer drug resistance; alternative mRNA splicing (AS) in cancer drug resistance; the interplay between AS and miRNA in chemoresistance will be discussed. Despite this great potential, the interplay between aberrant splicing events and miRNA is understudied but holds great potential in deciphering miRNA-mediated drug resistance.

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“…Because of the high expression level and stability of circRNA, it is used as a competitive endogenous RNA (ceRNA) 6 . circRNA competes with miRNA to prevent the posttranslational inhibition of miRNA and target coding RNA, ultimately regulating the expression levels of target genes 7 .…”

Section: Introductionmentioning

confidence: 99%

circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3

et al. 2021

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The abnormal expression of circular RNAs (circRNAs) is associated with numerous human diseases. This study investigated the mechanism by which circRNA acts as competitive endogenous RNA in the regulation of degenerative intervertebral disc disease (IVDD). Decreased expression of circSPG21 was detected in degenerated nucleus pulposus cells (NPCs), the function of circSPG21 in NPCs was explored and verified, and the downstream target of circSPG21 was investigated. The interaction between circSPG21 and miR-1197 and its target gene (ATP1B3) was studied by online database prediction and molecular biological verification. Finally, the circSPG21/miR-1197/ATP1B3 axis was verified in the mouse tail-looping model. The expression of circSPG21 in the nucleus pulposus in IVDD was directly related to an imbalance of anabolic and catabolic factors, which affected cell senescence. circSPG21 was found to play a role in human NPCs by acting as a sponge of miR-1197 and thereby affecting ATP1B3. The regulation of circSPG21 provides a potentially effective therapeutic strategy for IVDD.

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Coordinated AR and microRNA regulation in prostate cancer

Cited by 15 publications

References 177 publications

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

MicroRNA and Alternative mRNA Splicing Events in Cancer Drug Response/Resistance: Potent Therapeutic Targets

circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3

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