J Cancer 2020; 11(15):4550-4559. doi:10.7150/jca.45676 This issue Cite

Research Paper

Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p

Jun Shen1*, Jianhua Xiong2*, Xuefei Shao1*, Hao Cheng1, Xinyun Fang1, Yongkang Sun1, Guangfu Di1, Jie Mao3✉, Xiaochun Jiang1✉

1. Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College, Wuhu, P.R. China
2. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, P.R. China
3. Department of Neurosurgery, Shenzhen Hospital, Southern Medical University, Shenzhen, 518000, P.R. China
* Contributed equally to this work

Citation:
Shen J, Xiong J, Shao X, Cheng H, Fang X, Sun Y, Di G, Mao J, Jiang X. Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p. J Cancer 2020; 11(15):4550-4559. doi:10.7150/jca.45676. https://www.jcancer.org/v11p4550.htm
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Abstract

Background: Gliomas are the most prevalent primary malignant tumors of the central nervous system. Our previous study showed that miR-204-5p is a tumor suppressor gene in glioma. Bioinformatic analyses suggest that long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is a potential target gene of miR-204-5p.

Methods: We analyzed the expression of XIST and miR-204-5p in glioma tissues and the correlation with glioma grade. A series of in vitro experiments were carried out to elucidate the role of XIST in glioma progression. A mouse xenograft model was established to detect whether knockdown of XIST can inhibit glioma growth. A luciferase assay was performed to determine whether XIST can bind to miR-204-5p and the binding specificity. Cells stably expressing shXIST or shNC were transfected with anti-miR-204-5p or anti-miR-204-5p-NC to evaluate whether XIST mediates the tumor-suppressive effects of miR-204-5p.

Results: XIST was upregulated in glioma tissues compared with normal brain tissues (NBTs), while miR-204-5p expression was significantly decreased in glioma tissues compared with NBTs. Both XIST and miR-204-5p expression levels were clearly related to glioma grade, and the expression of XIST was obviously negatively correlated with miR-204-5p expression. Knockdown of XIST inhibited glioma cell proliferation, migration, and invasion, promoted apoptosis of glioma cells, inhibited tumor growth and increased the survival time in nude mice. miR-204-5p could directly bind to XIST and negatively regulate XIST expression. XIST mediated glioma progression by targeting miR-204-5p in glioma cells. XIST crosstalk with miR-204-5p regulated Bcl-2 expression to promote apoptosis.

Conclusion: Our results provide evidence that XIST, miR-204-5p and Bcl-2 form a regulatory axis that controls glioma progression and can serve as a potential therapeutic target for glioma.

Keywords: Knockdown, RNA XIST, glioma progression, miR-204-5p


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APA
Shen, J., Xiong, J., Shao, X., Cheng, H., Fang, X., Sun, Y., Di, G., Mao, J., Jiang, X. (2020). Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p. Journal of Cancer, 11(15), 4550-4559. https://doi.org/10.7150/jca.45676.

ACS
Shen, J.; Xiong, J.; Shao, X.; Cheng, H.; Fang, X.; Sun, Y.; Di, G.; Mao, J.; Jiang, X. Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p. J. Cancer 2020, 11 (15), 4550-4559. DOI: 10.7150/jca.45676.

NLM
Shen J, Xiong J, Shao X, Cheng H, Fang X, Sun Y, Di G, Mao J, Jiang X. Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p. J Cancer 2020; 11(15):4550-4559. doi:10.7150/jca.45676. https://www.jcancer.org/v11p4550.htm

CSE
Shen J, Xiong J, Shao X, Cheng H, Fang X, Sun Y, Di G, Mao J, Jiang X. 2020. Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p. J Cancer. 11(15):4550-4559.

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