Inhibition of Type 2 Transglutaminase significantly alters long noncoding RNAs expression in triplenegative breast cancer cell line.

Type 2 Transglutaminase (TG2) is an ubiquitously expressed enzyme involved in various physiological and pathological processes, strongly linked to cancer. One of its identified functions is serving as a regulator of gene expression by modifying histones through a process known as serotonylation, or interacting with transcription factors and other expression regulators. Albeit several steps forward have been achieved in the understanding of cancer mechanisms in the last years, long noncoding RNAs’ (lncRNAs) role in cancer is still debated. The aim of this study was the evaluation of long noncoding RNA expression in MDAMB436 triplenegative breast cancer (TNBC) cell line, after the selective inhibition of TG2 with AA9, a novel permeable inhibitor. The bulk RNA sequencing analysis has highlighted a significant deregulation of 558 lncRNAs, revealing the crucial role of TG2 in noncoding RNAs gene expression modulation. Notably, within the most deregulated lncRNAs, which has been selected based on log2 fold change values, some previously acknowledged cancerrelated lncRNAs were found significantly altered. For example, UPK1AAS1, which has been described as a marker of negative prognosis in pancreatic cancer patients, or the oncogenic SAP30DT, or MIR210HG, strongly linked to hypoxiarelated genes expression in breast cancer. These results confirms the involvement of TG2 in gene expression regulation, further suggesting its role in lncRNAs landscape modulation of TNBC cell line, which has never been deeply investigated so far.