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Related Concept Videos

RNA Splicing01:32

RNA Splicing

56.3K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Alternative RNA Splicing02:18

Alternative RNA Splicing

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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Master Transcription Regulators02:23

Master Transcription Regulators

6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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What is Gene Expression?01:36

What is Gene Expression?

8.5K
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.5K
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  9. Predictive And Prognostic Markers
  11. Androgen Receptor Splice Variants Drive Castration-resistant Prostate Cancer Metastasis By Activating Distinct Transcriptional Programs.
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Androgen Receptor Splice Variants Drive Castration-resistant Prostate Cancer Metastasis By Activating Distinct Transcriptional Programs.

Related Experiment Video

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

6.8K

Androgen receptor splice variants drive castration-resistant prostate cancer metastasis by activating distinct transcriptional programs.

Dong Han1,2, Maryam Labaf1,3,4, Yawei Zhao5

  • 1Center for Personalized Cancer Therapy.

The Journal of Clinical Investigation
|April 30, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Prostate cancer

Keywords:
Molecular geneticsOncologyProstate cancerTranscription

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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

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Related Experiment Videos

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer (PCa) treatment resistance often involves androgen receptor (AR) splice variants like AR-V7.
  • The distinct functions of AR-V7 compared to full-length AR (AR-FL) in castration-resistant PCa (CRPC) metastasis are not fully understood.

Purpose of the Study:

  • To elucidate the unique biological functions and metastatic role of AR-V7 in CRPC.
  • To investigate the molecular mechanisms by which AR-V7 drives metastasis, including chromatin accessibility and target gene activation.

Main Methods:

  • Overexpression of AR-V7 and AR-FL in castrated models.
  • Chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq), and RNA sequencing (RNA-seq).
  • Analysis of SOX9 regulation and AR-V7 phosphorylation at Ser81.
  • Inhibition studies using CDK9 inhibitors.

    • Main Results:

    • AR-V7, but not AR-FL, induced osteoblastic bone lesions in castrated conditions.
    • AR-V7 accessed compact chromatin regions, activating a distinct pro-metastatic transcription program enriched for epithelial-mesenchymal transition genes.
    • SOX9 was identified as a direct AR-V7 target, upregulated in AR-V7-induced bone lesions.
    • Ser81 phosphorylation enhanced AR-V7's pro-metastasis function; CDK9 inhibition disrupted this program.

    Conclusions:

    • AR-V7 drives CRPC bone metastasis through unique chromatin access and activation of specific gene programs, including SOX9.
    • AR-V7 Ser81 phosphorylation is a key regulator of its pro-metastasis activity, offering a potential therapeutic target.
    • These findings provide critical molecular insights into AR splice variant-driven CRPC progression.