@article{f36028b5565f49c0a956ca4b4d3038d5,
title = "A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression",
abstract = "Antisense RNAs are ubiquitous in human cells, yet their role is largely unexplored. Here we profiled antisense RNAs in the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one antisense RNA that drives cancer progression by upregulating the redox enzyme NADPH quinone dehydrogenase 1 (NQO1), and named it NQO1-AS. Knockdown of either NQO1 or NQO1-AS reduced lung colonization in a mouse model, and investigation into the role of NQO1 indicated that it is broadly protective against oxidative damage and ferroptosis. Breast cancer cells in the lung are dependent on this pathway, and this dependence can be exploited therapeutically by inducing ferroptosis while inhibiting NQO1. Together, our findings establish a role for NQO1-AS in the progression of breast cancer by regulating its sense mRNA post-transcriptionally. Because breast cancer predominantly affects females, the disease models used in this study are of female origin and the results are primarily applicable to females.",
author = "Bruce Culbertson and Kristle Garcia and Daniel Markett and Hosseinali Asgharian and Li Chen and Lisa Fish and Albertas Navickas and Johnny Yu and Brian Woo and Nanda, {Arjun Scott} and Benedict Choi and Shaopu Zhou and Joshua Rabinowitz and Hani Goodarzi",
note = "Funding Information: We acknowledge the UCSF Center for Advanced Technology and the Chan Zuckerberg Biohub for high-throughput sequencing and other genomic analyses. We thank B. Hann and the Preclinical Therapeutics core as well as the Laboratory Animal Resource Center at UCSF. We are also grateful for the genomic data contributed by the TCGA Research Network, including donors and researchers. We acknowledge support from our colleagues at the Helen Diller Family Comprehensive Cancer Center. We thank J. Massagu{\'e} (Memorial Sloan Kettering) and S. Tavazoie (The Rockefeller University) for gifting us the MDA-LM2 and HCC1806-LM2 cell lines, respectively. We also thank J. Weissman (Massachusetts Institute of Technology) and L. Gilbert (UCSF) for the CRISPRi and CRISPRa constructs. We thank B. R. Stockwell for his input on studying ferroptosis. We thank K. Yin and T. Joshi for their help with the experiments using the BT-20 cells. We thank X. Xu for his help with the analysis of the metabolic data. We also acknowledge the Ludwig Cancer Research Institute. D.M. was supported by an MD fellowship from the Boehringer Ingelheim Fonds. This work was supported by grants from the National Institutes of Health (NIH) (nos. R00CA194077 and R01CA24098) and American Chemical Society (no. 130920-RSG-17-114-01-RMC) to H.G., as well as grant no. R01CA163591 from the NIH to J.D.R. Funding Information: We acknowledge the UCSF Center for Advanced Technology and the Chan Zuckerberg Biohub for high-throughput sequencing and other genomic analyses. We thank B. Hann and the Preclinical Therapeutics core as well as the Laboratory Animal Resource Center at UCSF. We are also grateful for the genomic data contributed by the TCGA Research Network, including donors and researchers. We acknowledge support from our colleagues at the Helen Diller Family Comprehensive Cancer Center. We thank J. Massagu{\'e} (Memorial Sloan Kettering) and S. Tavazoie (The Rockefeller University) for gifting us the MDA-LM2 and HCC1806-LM2 cell lines, respectively. We also thank J. Weissman (Massachusetts Institute of Technology) and L. Gilbert (UCSF) for the CRISPRi and CRISPRa constructs. We thank B. R. Stockwell for his input on studying ferroptosis. We thank K. Yin and T. Joshi for their help with the experiments using the BT-20 cells. We thank X. Xu for his help with the analysis of the metabolic data. We also acknowledge the Ludwig Cancer Research Institute. D.M. was supported by an MD fellowship from the Boehringer Ingelheim Fonds. This work was supported by grants from the National Institutes of Health (NIH) (nos. R00CA194077 and R01CA24098) and American Chemical Society (no. 130920-RSG-17-114-01-RMC) to H.G., as well as grant no. R01CA163591 from the NIH to J.D.R. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = may,
doi = "10.1038/s43018-023-00554-7",
language = "English (US)",
volume = "4",
pages = "682--698",
journal = "Nature Cancer",
issn = "2662-1347",
publisher = "Nature Research",
number = "5",
}