Featured Research

from universities, journals, and other organizations

Likely key driver of colorectal cancer development, progression

Date:
April 14, 2014
Source:
Ohio State University Wexner Medical Center
Summary:
A molecule that is a probable driving force in colorectal cancer has been identified in a new study. The molecule could be an important target for colorectal cancer treatment and a valuable biomarker of tumor progression. The researchers demonstrate that miR-135b is present at abnormally high levels in both mouse and human colorectal (CRC) tumors. The overexpression can be induced by the mutations in either well-known oncogenes or tumor-suppressor genes that frequently occur in CRC, they say.

A new study identifies a molecule that is a probable driving force in colorectal cancer and suggests that the molecule could be an important target for colorectal cancer treatment and a valuable biomarker of tumor progression.

The study of microRNA-135b (miR-135b) in two animal models and human tumors was published in the journal Cancer Cell and was led by researchers at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) and at the University of Glasgow in the United Kingdom.

The researchers demonstrate that miR-135b is present at abnormally high levels in both mouse and human colorectal (CRC) tumors. The overexpression can be induced by the mutations in either well-known oncogenes or tumor-suppressor genes that frequently occur in CRC, the researchers say.

"We found that miR-135b is up-regulated in both sporadic and inflammatory bowel disease-associated colorectal cancer, and that its up-regulation is associated with tumor stage and poor clinical outcome," says principal investigator Carlo M. Croce, MD, chair of molecular virology, immunology and medical genetics, and director of Human Cancer Genetics at Ohio State and the OSUCCC -- James.

"Our findings provide proof-of-principle that anti-miR-135b has significant therapeutic potential in colorectal cancer treatment," says Croce, who is also the John W. Wolfe Chair in Human Cancer Genetics.

For this study, Croce and his collaborators used a CRC mouse model based on loss of a tumor suppressor and a model based on inflammation and oncogene activation; human tumors from a cohort of sporadic CRC and inflammatory-bowel-disease associated CRC; human and animal cell lines and data from The Cancer Genome Atlas.

Key findings included:

  • MiR-135b up-regulation occurs in both sporadic and inflammatory bowel disease-associated CRC, and it is associated with tumor stage and poor clinical outcome;
  • Loss of the APC gene, deregulation of the PTEN/PI3K pathway and over-expression of the SRC oncogene all trigger miR-135b over-expression;
  • Artificial miR-135b over-expression increases cell proliferation and reduces apoptosis, as occurs with APC loss or PI3K or SRC activation.
  • Delivering anti-miR-135b in an inflammation-related CRC mouse model affected proliferation and apoptosis, resulting in reduced tumor number and size.

Story Source:

The above story is based on materials provided by Ohio State University Wexner Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nicola Valeri, Chiara Braconi, Pierluigi Gasparini, Claudio Murgia, Andrea Lampis, Viola Paulus-Hock, JonathanR. Hart, Lynn Ueno, SergeiI. Grivennikov, Francesca Lovat, Alessio Paone, Luciano Cascione, KhleaM. Sumani, Angelo Veronese, Muller Fabbri, Stefania Carasi, Hansjuerg Alder, Giovanni Lanza, Roberta Gafa’, MaryP. Moyer, RachelA. Ridgway, Julia Cordero, GerardJ. Nuovo, WendyL. Frankel, Massimo Rugge, Matteo Fassan, Joanna Groden, PeterK. Vogt, Michael Karin, OwenJ. Sansom, CarloM. Croce. MicroRNA-135b Promotes Cancer Progression by Acting as a Downstream Effector of Oncogenic Pathways in Colon Cancer. Cancer Cell, 2014; 25 (4): 469 DOI: 10.1016/j.ccr.2014.03.006

Cite This Page:

Ohio State University Wexner Medical Center. "Likely key driver of colorectal cancer development, progression." ScienceDaily. ScienceDaily, 14 April 2014. <www.sciencedaily.com/releases/2014/04/140414123743.htm>.
Ohio State University Wexner Medical Center. (2014, April 14). Likely key driver of colorectal cancer development, progression. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2014/04/140414123743.htm
Ohio State University Wexner Medical Center. "Likely key driver of colorectal cancer development, progression." ScienceDaily. www.sciencedaily.com/releases/2014/04/140414123743.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins