MicroRNAs (miRNAs) encode small RNAs that regulate gene expression. These are useful to improve classification, diagnostic and prognostic information for cancer. Liu and colleagues conducted a study to identify miRNAs that are overexpressed in lung cancers compared with those of normal lung tissues, and to identify those that function as cancer-promoting miRNAs.
The researchers identified functionally important miR-31 target genes that included two tumor suppressors: large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A). Expression of miR-31 was inversely related to LATS2 and PPP2R2A in both mouse and human lung cancers, according to Liu.
In a validation study, researchers detected 10 abundantly overexpressed miRNAs in a mouse model, then used human lung cancers to determine whether the same 10 were overexpressed. Findings showed three miRNAs were significantly overexpressed ??” miR-31, miR-136 and miR-376a.
"It was surprising that knock-down of only miR-31 repressed growth of mouse and human lung cancer cells and inhibited lung cancer formation in mice," Liu said.
Additionally, the tumor suppressors were repressed by miR-31 overexpression and substantially increased by miR-31 knock-down, which is a good predictor of loss of oncogenicity, according to Liu.
4033. MiR-21 upregulation in breast cancer cells leads to PTEN loss and Herceptin resistance
Scientists at the University of Texas M. D. Anderson Cancer Center have identified a microRNA (miRNA) that could potentially separate the patients who will respond to Herceptin from those who will not.
Herceptin was approved to treat HER2 positive breast cancer in 1998 and is considered by many to be a revolutionary therapy. However, only about 35 percent of patients who receive Herceptin as a single agent will respond to the therapy.
"If we know in advance who is going to respond to treatment, then this could possibly save patients from undergoing this treatment unnecessarily," said Sumaiyah K. Rehman, a third-year graduate student in the lab of Dihua Yu, M.D., Ph.D., Hubert L. and Olive Stringer distinguished chair in basic science, professor and deputy chair of the department of molecular and cellular oncology and director of the cancer biology program at the University of Texas M. D. Anderson Cancer Center.
Herceptin has been linked with heart problems in 2 percent to 7 percent of cases, and patients often have to weigh the risk of heart disorders against the risk of their continuing cancer.
In the current study, scientists found that breast cancer cells with increased miR-21 and reduced PTEN expression were significantly more resistant to Herceptin than control cells. PTEN loss had been previously linked to Herceptin resistance in another study published from the same group and confirmed by other research groups.
The scientists further tested this finding in patients and found that high levels of miR-21 were significantly correlated with poor response to Herceptin. Rehman said she would continue her study to better understand the mechanisms of miR-21-mediated resistance.
"MiRNAs have been reported to control up to 35 percent of our genome, so there are many discoveries remaining," said Rehman. "This is one drop of information in the bucket of knowledge that is hardly full in what we can learn."
Source: American Association for Cancer Research