Nav: Home

Characterization of unique PMEPA1 gene splice variants (isoforms d and e) from RNA Seq profiling pro

January 31, 2020

The cover for issue 4 of Oncotarget features Figure 8, "Model for biological function categorization of PMEPA1 isoforms (c, d, and e) in the context of prostate cancer," by Sharad, et al.

In addition to 4 reported PMEPA1 isoforms, one novel isoform PMEPA1-e was identified with RNA Seq analysis of hormone-responsive VCa P, LNCa P cells and human prostate cancer samples from The Cancer Genome Atlas dataset.

The researchers analyzed the structures, expressions, biological functions and clinical relevance of PMEPA1-e isoform and less characterized isoforms c and d in the context of prostate cancer and AR/TGF- signaling.

The expression of PMEPA1-e was induced by androgen and AR.

Taken together, their findings first defined the prostate tumorigenesis mediated by PMEPA1-d and -e isoforms, providing novel insights into the new strategies for prognostic evaluation and therapeutics of prostate tumor.

Dr. Hua Li and Dr. Shashwat Sharad from the Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences as well as the Walter Reed National Military Medical Center, Bethesda, Maryland, USA said in their Oncotarget article, "Prostate cancer is the most commonly diagnosed male malignancy and second leading cause of cancer-related deaths in the USA."

It was shown that the methylation of PMEPA1 gene promoter accounted for the silencing of PMEPA1 in prostate cancer cells in vitro and in vivo.

PMEPA1 was also reported as a TGF- regulated gene in the context of both prostate cancer and non-prostate solid tumors including colon, lung and breast cancers.

Further, a recent study showed that the loss of membrane-anchored PMEPA1 protein facilitated metastasis of prostate cancer via activating TGF- signaling by sequestering SMAD2/3 in proteasome independent way.

Cumulatively, these findings underscored the multi-function features of the PMEPA1 gene and further suggested its expressions and biological functions were dependent on the cellular context centering androgen and TGF- signaling.

The alternative splicing variant mechanism had also been shown to be important for diversifying functions of tumor-associated genes.

Further, earlier studies from their and other groups explored PMEAP1 gene isoforms in the initiation and development of prostate tumors via interrupting AR and/or TGF- signaling.

Here, the Oncotarget authors focused on defining the expressions, regulations and biological behaviors/functions of understudied PMEPA1 isoforms in the context of both androgen and TGF- signaling, and further exploration of the clinical significances and relevance of these isoforms in prostate tumor.

The Li/Sharad Research Team concluded in their Oncotarget study that gene isoform ratio could potentially predict the gene functional consequences and disease progression.
-end-
Sign up for free Altmetric alerts about this article

Full text - https://doi.org/10.18632/oncotarget.27406

Correspondence to - Hua Li - hli@cpdr.org and Shashwat Sharad - ssharad@cpdr.org

Keywords - prostate cancer, PMEPA1, gene isoform, splice variant, TGF-β

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with @Oncotarget

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact

18009220957x105
MEDIA@IMPACTJOURNALS.COM

Impact Journals LLC

Related Prostate Cancer Articles:

ESMO 2020: Breast cancer drug set to transform prostate cancer treatment
A drug used to treat breast and ovarian cancer can extend the lives of some men with prostate cancer and should become a new standard treatment for the disease, concludes a major trial which is set to change clinical practice.
Major trial shows breast cancer drug can hit prostate cancer Achilles heel
A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.
The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.
Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.
First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.
Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.
CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.
Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
More Prostate Cancer News and Prostate Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.