RT Journal Article SR Electronic T1 A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.08.463652 DO 10.1101/2021.10.08.463652 A1 Bruce Culbertson A1 Kristle Garcia A1 Daniel Markett A1 Hosseinali Asgharian A1 Li Chen A1 Lisa Fish A1 Albertas Navickas A1 Johnny Yu A1 Brian Woo A1 Scott Nanda A1 Joshua Rabinowitz A1 Hani Goodarzi YR 2021 UL http://biorxiv.org/content/early/2021/10/09/2021.10.08.463652.abstract AB Antisense RNAs are ubiquitous in human cells, yet the role that they play in healthy and diseased states remains largely unexplored. Here, we developed a computational framework to catalog and profile antisense RNAs and applied it to poorly and highly metastatic breast cancer cell lines. We identified one antisense RNA that plays a functional role in driving breast cancer progression by upregulating the redox enzyme NQO1, and hence named NQO1-antisense RNA or NQO1-AS. This upregulation occurs via a stabilizing interaction between NQO1-AS and its complementary region in the 3’UTR of NQO1 mRNA. By increasing expression of NQO1 protein, breast cancer cells are able to tolerate higher levels of oxidative stress, enabling them to colonize the lung. During this process the cancer cells become dependent on NQO1 to protect them from ferroptosis. We have shown that this dependence can be exploited therapeutically in xenograft models of metastasis. Together, our findings establish a previously unknown role for NQO1-AS in the progression of breast cancer by serving as a post-transcriptional regulator of RNA processing and decay for its sense mRNA.Competing Interest StatementThe authors have declared no competing interest.