A new Australian study has provided further insights into the molecular mechanisms underlying breast cancer. More importantly, the research identified an exploitable Achilles' heel that may lead to the development of a more effective, targeted treatments.
Breast cancer is the world’s most prevalent cancer, overwhelmingly affecting women. The World Health Organization (WHO) reports that, at the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the previous five years. It’s estimated that 5% to 10% of breast cancers are linked to genetic mutations that are passed down through family generations.
All biological molecules – RNA, DNA, proteins, sugars, and fats – are subject to modifications. RNA, particularly, carries an array of chemical modifications that play important roles in the regulation of gene expression. The methylation of RNA to form N6-methyladenosine (m6A) is the most prevalent internal modification of messenger RNAs (mRNAs). Methylation is a chemical process where a small molecule (methyl group) gets added to DNA, proteins, or other molecules and changes how they act. RNA methylation has been linked to cancer and is facilitated by the interplay of methylation-specific proteins.
Researchers from the Centenary Institute in Sydney, Australia, have focused on the role of one of these proteins, Virilizer-like methyltransferase or VIRMA, in breast cancer.
The researchers injected mice with breast cancer cells and monitored the animals twice weekly, assessing body condition and measuring body weight and tumor size. Then the tumors were examined, and the mice’s VIRMA levels were measured.
They found that a distinct variant of VIRMA, found within the nucleus of the cell, is amplified and overexpressed in 15% to 20% of breast cancers. VIRMA promotes the growth of breast cancer cells by influencing RNA methylation. In addition, the researchers identified a non-coding RNA molecule called NEAT1, which they found interacted with VIRMA to promote cancer cell growth, causing the progression of the disease.
As well as providing greater insight into the molecular mechanisms underlying breast cancer, the research had an even better upside. In the course of examining the VIRMA-overexpressing breast cancer cells, the researchers discovered that they were susceptible to stress, which caused them to die. These stressful conditions – for example, hypoxia or low oxygen levels – are often present in tumor microenvironments and, the researchers say, might be an Achilles' heel that can be exploited when developing new, targeted cancer treatments.
“Based on our findings, we can repurpose certain therapeutic drugs that trigger stress response to target and eliminate breast cancer cells that have high levels of VIRMA,” said Justin Wong, corresponding author of the study. “By targeting VIRMA-overexpressed cancer cells, the aim is to enhance stress response in cancer cells and ultimately force them to commit suicide.”
The study was published in the journal Cellular and Molecular Life Sciences.
Source: Centenary Institute
