A new perspective on carcinogenesis: miRNA 15a/16–1 cluster deletions promote cell survival via Protein L-isoaspartate O-methyltransferase (PCMT1) activity

Cancer is a commonly encountered disease both in Turkey and worldwide. Cellular gene expression profiles that drastically change during carcinogenesis can be regulated via several epigenetic mechanisms such as DNA methylation, non-coding RNAs (ncRNA), RNA interference (RNAi), histone variants and post-translational modifications of histones. In addition to these mechanisms, genetic anomalies that arise due to various reasons including mutations, deletions and translocations have significant roles both in carcinogenesis and the response to treatment and are screened routinely in clinic when determining cancer subtypes. miRNA 15a/16-1 cluster which is located on the q arm of chromosome 13 is often deleted in cancers and regulates the activity of several cancer-associated genes such as Mcl1, Bcl2, Ets1, Jun. Furthermore, the role of Protein L-isoaspartate O-methyltransferase (PCMT1) which is regulated by these miRNAs, in carcinogenesis through its effects in apoptosis pathway is emphasized by various studies. It is suggested that there is a feedback loop between miRNA 15a/16-1 cluster and p53 which regulates cellular signals for proliferation and cell survival. Studies describe miRNA 15a/16-1 cluster as a tumor suppressor, while identifying PCMT1 as an oncogene. In line with this, deletions in the 13q14.3 region which also spans the miRNA 15a/16-1 cluster are detected in multiple lymphoid and myeloid leukemia subtypes and have the potential to be included in routine clinical genetic screens. Examining 13q14.3 deletions in leukemia patients has the potential to yield important results that could be useful both in determining cancer subtypes and deciding which therapeutic regime to apply on a single-patient basis