Loss of a Specific MicroRNA Leads to Growth and Spread of Pancreatic Cancer

Cancer researchers have found that the loss of a specific microRNA (miRNA) enables pancreatic cancer cells to avoid the tumor suppressor pathways that induce senescence and induces them go grow and spread.

MicroRNAs are a class of about 20 nucleotides-long RNA fragments that block gene expression by attaching to molecules of messenger RNA in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA. With their capacity to fine-tune protein expression via sequence-specific interactions, miRNAs help regulate cell maintenance and differentiation.

Investigators at the University of Montreal (Canada) reported in the February 18, 2016, online edition of the journal Cell Reports that pancreatic tumors often lost the ability to express the microRNA miR-137. They found that miR-137 targeted the messenger RNA responsible for translating the enzyme KDM4A (lysine-specific demethylase 4A) during Ras-induced senescence. Loss of KDM4A expression through inhibition by miR-137 activated both the p53 and the retinoblastoma (pRb) tumor suppressor pathways.

Restoring KDM4A expression by removing miR-137 enabled the cancer cells to avoid senescence. In contrast, restoration of miR-137 expression inhibited pancreatic cancer cell proliferation and promoted senescence.

"It is essential that we better understand the mechanisms that lead to the loss of miR-137 expression. Once we do, we can create therapeutic strategies to treat and prevent pancreatic cancer," said senior author Dr. Frédérick Antoine Mallette, assistant professor of immunology and oncology at the University of Montreal.

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