Y chromosome LncRNA are involved in radiation response of male non-small cell lung cancer cells

Tayvia Brownmiller, Jamie A. Juric, Abby D. Ivey, Brandon M. Harvey, Emily S. Westemeier, Michael T. Winters, Alyson M. Stevens, Alana N. Stanley, Karen E. Hayes, Samuel A. Sprowls, Amanda S. Gatesman Ammer, Mackenzee Walker, Erik A. Bey, Xiaoliang Wu, Zuan Fu Lim, Lin Zhu, Sijin Wen, Gangqing Hu, Patrick C. Ma, Ivan Martinez

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Numerous studies have implicated changes in the Y chromosome in male cancers, yet few have investigated the biological importance of Y chromosome noncoding RNA. Here we identify a group of Y chromosome-expressed long noncoding RNA (lncRNA) that are involved in male non-small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive male NSCLC cell lines demonstrated a dose-dependent induction of linc-SPRY3-2/3/4 following irradiation, which was not observed in radioresistant male NSCLC cell lines. Cytogenetics revealed the loss of chromosome Y (LOY) in the radioresistant male NSCLC cell lines. Gain- and loss-of-function experiments indicated that linc-SPRY3-2/3/4 transcripts affect cell viability and apoptosis. Computational prediction of RNA binding proteins (RBP) motifs and UV-cross-linking and immunoprecipitation (CLIP) assays identified IGF2BP3, an RBP involved in mRNA stability, as a binding partner for linc-SPRY3-2/3/4 RNA. The presence of linc-SPRY3-2/3/4 reduced the half-life of known IGF2BP3 binding mRNA, such as the antiapoptotic HMGA2 mRNA, as well as the oncogenic c-MYC mRNA. Assessment of Y chromosome in NSCLC tissue microarrays and expression of linc-SPRY3-2/3/4 in NSCLC RNA-seq and microarray data revealed a negative correlation between the loss of the Y chromosome or linc-SPRY3-2/3/4 and overall survival. Thus, lincSPRY3-2/3/4 expression and LOY could represent an important marker of radiotherapy in NSCLC.

Original languageEnglish (US)
Pages (from-to)4046-4057
Number of pages12
JournalCancer Research
Issue number19
StatePublished - Oct 1 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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