Abstract
Tudor domain containing protein 9 (TDRD9) is a RNA helicase normally expressed in the germline, where it is involved in the biosynthesis of PIWI-interacting RNAs (piRNAs). Here, we show that TDRD9 is highly expressed in a subset of non-small cell lung carcinomas and derived cell lines by hypomethylation of its CpG island. Furthermore, TDRD9 expression is associated with poor prognosis in lung adenocarcinoma. We find that downregulation of TDRD9 expression in TDRD9-positive cell lines causes a decrease in cell proliferation, S-phase cell cycle arrest, and apoptosis. Transcriptomic analysis demonstrated that TDRD9 knockdown causes upregulation of cell cycle and DNA repair genes. We also observed that TDRD9 knockdown triggers activation of the catalytic subunit of the DNA dependent protein kinase (DNA-PKcs) and phosphorylation of H2A.X, which are indicative of an increase of DNA double strand breaks. TDRD9-silenced cells also presented aberrant mitosis and abnormal-shaped nuclei indicating defects in chromosomal segregation. Finally, TDRD9 silencing caused hypersensitivity to the replication stress inducer aphidicolin, while overexpression of the protein increased resistance to the drug, suggesting that TDRD9 protects from replicative stress to TDRD9-positive tumor cells. Thus, our results place TDRD9 as a marker for prognosis and as a potential therapeutic target in a subset of lung carcinomas.
Highlights
Tudor domain containing protein 9 (TDRD9) is a putative ATP-dependent DEXH-box RNA helicase that contains a TUDOR domain [1, 2]
We show that the hypomethylation of the CpG island of TDRD9 leads to its expression in a subset of lung adenocarcinoma (LA) and non-small-cell lung carcinoma (NSCLC) tumors and cell lines
We found that TDRD9 expression is associated to poor prognosis for persons with LA
Summary
Tudor domain containing protein 9 (TDRD9) is a putative ATP-dependent DEXH-box RNA helicase that contains a TUDOR domain [1, 2]. Human TDRD9 is predominantly expressed in the germline. Mice Tdrd has been detected in spermatogonia, spermatocytes, spermatids in the testis and oocytes in the ovary [2]. Mammalian TDRD9 and the Drosophila homologue Spindle-E are involved in the process of biogenesis of a conserved class of small RNAs, called piRNA for their association with PIWI proteins [2,3,4,5,6,7]. Tdrd is essential for silencing Line-1 retrotransposons in the mouse male germline [2]. Tdrd knockout mice display male sterility, probably as a consequence of massive Line-1 activation.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
