Abstract 2450: The importance of a family of long noncoding RNAs from the Y chromosome in radiotherapy and chemotherapy response of male non-small cell lung cancer

Lung cancer is the number one cause of cancer-related deaths in the United States. The 5-year overall survival rate for patients with non-small cell lung cancer (NSCLC) stands at 18%, with women having a twice better overall survival rate than men. Currently, there is no solid evidence to explain the disparity between gender survival rates. The protein coding genes of the X and Y chromosomes have been relatively well characterized, and previous studies have implicated phenomena such as the dysregulation of X inactivation and the loss of the Y chromosome in a number of cancers. However, the regions of these chromosomes responsible for producing noncoding RNAs (ncRNAs) are not well understood. One such class of ncRNAs are long noncoding RNAs (lncRNAs), which are primarily classified as larger than 200 nucleotides and carry out functions in nearly every cellular process via a variety of mechanisms. In this study, we have identified a novel family of Y chromosome-linked lncRNAs that we hypothesize play a role in NSCLC cell survival. Our preliminary data show a time- and dose-dependent response in expression of the Y chromosome lncRNA family after radiation in radiosensitive NSCLC cell lines but not in radioresistant NSCLC cell lines, and we see a similar trend in response to cisplatin. Additionally, upon knockdown of this family in a sensitive cell line using two different shRNAs, we immediately observed an increase in proliferation of the knockdown cells when compared to shCtrl as well as increased cell viability and resistance to apoptosis in response to radiation, and increased resistance to cisplatin. We plan to further characterize these lncRNAs using methods such as qRT-PCR, virtual Northern blotting, traditional Northern blotting, direct RNA sequencing, cellular fractionation, and fluorescent in situ hybridization and determine their function by shRNA knockdown and subsequent assays to measure cellular processes in response to radiation and chemotherapy. The Identification of a male-specific component of lung cancer would fill a knowledge gap that could provide potential therapeutic targets and new prognostic factors, thereby improving the response rate of men with NSCLC. Citation Format: Tayvia Brownmiller, Jamie Barr, Abby Harold, Erik Bey, Ivan Martinez. The importance of a family of long noncoding RNAs from the Y chromosome in radiotherapy and chemotherapy response of male non-small cell lung cancer [abstract]. In: Proceedings of the American Associ