Long Non-coding RNA MALAT1 Upregulates ZEB2 Expression to Promote Malignant Progression of Glioma by Attenuating miR-124
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ORIGINAL PAPER
Long Non-coding RNA MALAT1 Upregulates ZEB2 Expression to Promote Malignant Progression of Glioma by Attenuating miR-124 Hongyu Cheng 1 & Haikang Zhao 2 & Xin Xiao 3 & Qian Huang 4 & Wen Zeng 5 & Bo Tian 5 & Tao Ma 5 & Dan Lu 5 & Yulong Jin 6 & Yuqian Li 5 Received: 20 March 2020 / Accepted: 9 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to play a critical role in the development of several malignancies. However, the potential molecular mechanism of MALAT1 in glioma remains unclear. In the present study, we found that the expression of MALAT1 was aberrantly increased in both human glioma tissues and cells and associated with poor prognosis in glioma patients. We further found that MALAT1 silencing significantly inhibited glioma cell proliferation while induced cell cycle arrest and apoptosis. In parallel, knockdown of MALAT1 decreased tumor volume in vivo. These results suggested that MALAT1 acts as a functional oncogene, resulting in the oncogenicity in glioma. Nevertheless, the tumor-suppressive effect of MALAT1 silencing was reversed by miR-124. Besides, the relevance of ZEB2 in tumor progression has been studied in several forms of human cancer, and ZEB2 was identified as a target of miR-124 and negatively regulated by miR-124. MALAT1 overexpression or miR-124 inhibitor led to increased expression of ZEB2. In summary, our study depicts a novel pathway of MALAT1/miR-124/ZEB2 that regulates the progression of glioma and might provide a promising strategy for glioma therapy. Keywords LncRNA . MALAT1 . miR-124 . ZEB2 . Glioma
Abbreviations lncRNA Long non-coding RNA MALAT1 Metastasis-associated lung adenocarcinoma transcript 1 WHO World Health Organization NEAT2 Nuclear-enriched abundant transcript 2
miRNAs 3’-UTR NHA DMEM FBS qRT-PCR
MicroRNAs 3’-untranslated region Normal human astrocytes Dulbecco’s modified Eagle’s medium Fetal bovine serum Quantitative real-time PCR
Hongyu Cheng, Haikang Zhao and Xin Xiao contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02165-0) contains supplementary material, which is available to authorized users. * Yulong Jin [email protected]
3
Department of Orthopedics, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, China
4
College of Basic Medicine, Air Force Medical University, Xi’an, Shaanxi, China
Department of Ultrasound Diagnosis, Tangdu Hospital, Air Force Medical University, No.1, Xinsi Road, Xi’an 710038, Shaanxi, China
5
Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
Department of Neurosurgery, The Second Hospital Affiliated of Xi’an Medical University, Xi’an, Shaanxi, China
6
Department of Hematology, General Hospital of Central Theater Command, Wuhan 430030, Hubei, China
* Yuqian Li [email protected] 1
2
Mol Neurobiol
NBT NC sh-MALAT1
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