The RNA-binding protein DDX1 promotes primary microRNA maturation and inhibits ovarian tumor progression
Authors: Cecil Han
Xinna Zhang
Anil K Sood
Yunhua Liu
Cristina Ivan
Xiongbin Lu
Luqing Zhao
Guohui Wan
Xiaoming He
Hyun Jin Choi
Journal: Cell Reports (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Posttranscriptional maturation; microRNA biogenesis; Drosha; DGCR8; regulatory RNA-binding proteins
Affiliations: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA., Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: ., Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: .

Abstract:  Posttranscriptional maturation is a critical step in microRNA (miRNA) biogenesis that determines mature miRNA levels. In addition to core components (Drosha and DGCR8 [DiGeorge syndrome critical region gene 8]) in the microprocessor, regulatory RNA-binding proteins may confer the specificity for recruiting and processing of individual primary miRNAs (pri-miRNAs). Here, we identify DDX1 as a regulatory protein that promotes the expression of a subset of miRNAs, including five members in the microRNA-200 (miR-200) family and four miRNAs in an eight-miRNA signature of a mesenchymal ovarian cancer subtype. A majority of DDX1-dependent miRNAs are induced after DNA damage. This induction is facilitated by the ataxia telangiectasia mutated (ATM)-mediated phosphorylation of DDX1. Inhibiting DDX1 promotes ovarian tumor growth and metastasis in a syngeneic mouse model. Analysis of The Cancer Genome Atlas (TCGA) reveals that low DDX1 levels are associated with poor clinical outcome in patients with serous ovarian cancer. These findings suggest that DDX1 is a key modulator in miRNA maturation and ovarian tumor suppression. 

Retracted: No

PubPeer comments:
 ![file] , 
 #2 Thank you for pointing out this error. We also noticed it after the paper was published, and thus submitted a corrigendum as well as the experimental details to Cell Reports. The editor received them. For more details, please contact the corresponding author (Xiongbin Lu, xiolu@iu.edu) or the first author (Cecil Han, ch1182@georgetown.edu). , 
 This does not appear to have been corrected, perhaps due to the fact that the last authoru2019s email address is no longer current. , 
 #4 Thank you for your reminder. We did communicate with the handling editor of Cell Reports and sent a corrigendum to the journal immediately after the error was found. As I recalled, we never received a reply. Attached is the file of corrigendum dated as March 12, 2015 in my computer. ![file] , 
 #5 thank you for responding. How do you explain the different signal and cropping? This seems deliberate rather than an error during figure assembly. , 
 https: forbetterscience.com 2021 04 19 xiongbin-lu-nanobombs-cancer-with-fluorescent-nude-mouse-recycling Indiana University Research Integrity Officer Shelley Bizila u201cMy office, IUu2019s Research Integrity Office, is responsible for receiving any allegations of possible falsification, fabrication or plagiarism and for administering IUu2019s policy. As such, our office has previously been made aware of the concerns you cite and has already started an inquiry process. We will proceed according to our policy to ensure any concerns of possible research misconduct are addressed. u201c , 
 No correction yet for this article as of 19 October 2022. In addition, could the authors perhaps clarify the similarities between panels I and III in Figure 6D? The caption of the figure states  *Representative images of tumor nodules and metastases in the mice carrying syngeneic ovarian tumors derived from control and DDX1-knockdown IG10 cells. Shown here are tumor mass in omentum of a control tumor (I) and tumor mass in omentum (II), perihepatic area (III), mesentery (IV), lymph nodes (V), and diaphragm (VI) of DDX1-knockdown tumors.* I interpreted this as that panel I was from a *control* tumor and panel III was from a *DDX-1 knockdown* tumor. Are these supposed to be from different mice or was the same mouse carrying both tumors? Maybe I am misunderstanding something. Some clarification would be appreciated. To me, these panels look like showing the same mice, albeit in slightly different phases of disection. ![file] , 
 Thank you for your question. Figure 6 legend is correctly stated. Figure 6D panel (I) is a representative image from the control mice (Mice injected IG10 cells stably expressing shNon-specific RNA as a control). In Figure 6D panels (II-VI) were from the DDX1X KD mice group (IG10 tumor with DDX1 shRNA expressing). In the perihepatic area from DDX1 KD mice (III), the image shows a distinctive tumor, and we did not find any tumor mass in the perihepatic area from the control mouse group. , 
 Thank you, Dr. Han, for the clarification. So, given that panels I and III are representing different mice, how would you explain the similarities in skin flaps, gut curvatures, and light reflections between these two panels? ,