Study identifies a likely key driver of colorectal cancer development and progression

April 14, 2014

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 , and that its up-regulation is associated with 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 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 number and size.

Related Stories

Study reveals mechanism of lung-cancer drug resistance

January 19, 2012

New research published in Nature Medicine indicates that targeted drugs such as gefitinib might more effectively treat non-small cell lung cancer if they could be combined with agents that block certain microRNAs.

Serum miR-21 putative biomarker for colorectal cancer

June 20, 2013

(HealthDay)—The oncogenic microRNA (miRNA) miR-21 is a potential biomarker for detection and prognosis of colorectal cancer (CRC), according to a study published in the June 19 issue of the Journal of the National Cancer ...

Recommended for you

Study reveals new insight into DNA repair

August 3, 2015

DNA double-strand breaks (DSBs) are the worst possible form of genetic malfunction that can cause cancer and resistance to therapy. New information published this week reveals more about why this occurs and how these breaks ...

Strange circular DNA may offer new way to detect cancers

July 30, 2015

Strange rings of DNA that exist outside chromosomes are distinct to the cell types that mistakenly produced them, researchers have discovered. The finding raises the tantalizing possibility that the rings could be used as ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.