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Theranostics 2021; 11(9):4516-4530. doi:10.7150/thno.54549 This issue Cite

Research Paper

LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis

Yansheng Li1,2*, Xing Liu3*, Xiaoteng Cui1*, Yanli Tan4, Qixue Wang1, Yunfei Wang1, Can Xu4, Chuan Fang5✉, Chunsheng Kang1✉

1. Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
2. Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, 20 Yudong Road, Yantai, Shandong 264001, P.R. China.
3. Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
4. Department of Pathology, Affiliated Hospital of Hebei University, Baoding 071000, China.
5. Department of Neurosurgery, Hebei University affiliated Hospital, Baoding 071000, China.
* Yansheng Li, Xing Liu and Xiaoteng Cui contributed equally to this work.

✉ Corresponding authors: Chunsheng Kang: kang97061edu.cn; Chuan Fang: fangchuan103com.

Citation:
Li Y, Liu X, Cui X, Tan Y, Wang Q, Wang Y, Xu C, Fang C, Kang C. LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics 2021; 11(9):4516-4530. doi:10.7150/thno.54549. https://www.thno.org/v11p4516.htm
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Abstract

Graphic abstract

Rationale: Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in cancer progression; however, only few have been characterized in detail. The current study aimed to identify a novel cancer driver lncRNA in glioblastoma and colon adenocarcinoma.

Methods: We performed whole transcriptome analysis of TCGA pan-cancer datasets to compare the lncRNA expression profiles of tumor and paired normal tissues. In situ hybridization of tissue sections was performed to validate the expression data and determine the localization of lncRNAs that may be linked to glioblastoma and colon adenocarcinoma. Chromatin isolation by RNA purification (ChIRP), chromatin immunoprecipitation (ChIP), and Co-immunoprecipitation (Co-IP) assays were performed to assess the interaction between lncRNA, proteins, and chromatin. The functional significance of the identified lncRNAs was verified in vitro and in vivo by knockdown or exogenous expression experiments.

Results: We found a lncRNA ENST00000449248.1 termed PRC2 and DDX5 associated lncRNA (PRADX) that is highly expressed in glioblastoma and colon adenocarcinoma cells and tissues. PRADX, mainly located in the nucleus of tumor cells, could bind to EZH2 protein via the 5' terminal sequence. Moreover, PRADX increased the trimethylation of H3K27 in the UBXN1 gene promoter via PRC2/DDX5 complex recruitment and promoted NF-κB activity through UBXN1 suppression. Knockdown of PRADX significantly inhibited tumor cell viability and clonogenic growth in vitro. In xenograft models, PRADX knockdown suppressed tumor growth and tumorigenesis and prolonged the survival of tumor-bearing mice.

Conclusions: PRADX acts as a cancer driver and may serve as a potential therapeutic target for glioblastoma and colon adenocarcinoma.

Keywords: PRADX, long noncoding RNA, glioblastoma, colon adenocarcinoma, NF-κB, TCGA, Polycomb repressive complex 2, DEAD box protein 5.

Citation styles

APA
Li, Y., Liu, X., Cui, X., Tan, Y., Wang, Q., Wang, Y., Xu, C., Fang, C., Kang, C. (2021). LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics, 11(9), 4516-4530. https://doi.org/10.7150/thno.54549.

ACS
Li, Y.; Liu, X.; Cui, X.; Tan, Y.; Wang, Q.; Wang, Y.; Xu, C.; Fang, C.; Kang, C. LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics 2021, 11 (9), 4516-4530. DOI: 10.7150/thno.54549.

NLM
Li Y, Liu X, Cui X, Tan Y, Wang Q, Wang Y, Xu C, Fang C, Kang C. LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics 2021; 11(9):4516-4530. doi:10.7150/thno.54549. https://www.thno.org/v11p4516.htm

CSE
Li Y, Liu X, Cui X, Tan Y, Wang Q, Wang Y, Xu C, Fang C, Kang C. 2021. LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics. 11(9):4516-4530.

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