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Article

NEAT1 is Required for the Expression of the Liver Cancer Stem Cell Marker CD44

1
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan
2
Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan
3
Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 1927; https://doi.org/10.3390/ijms21061927
Received: 9 December 2019 / Revised: 14 February 2020 / Accepted: 10 March 2020 / Published: 11 March 2020
(This article belongs to the Section Molecular Oncology)
CD44, a cancer stem cell (CSC) marker, is required for maintaining CSC properties in hepatocellular carcinoma (HCC). Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), is an oncogenic driver in HCC. In the present study, we investigated the significance of the NEAT1 gene in association with CD44 expression in liver CSCs of human HCC cell lines. The CSC properties were evaluated by spheroid culture, CSC marker expression, and sensitivity to anti-cancer drugs. The expression of both NEAT1 variant 1 (NEAT1v1) and variant 2 (NEAT1v2) as well as CD44 was significantly increased in the spheroid culture, compared with that in monolayer culture. Overexpression of Neat1v1, but not Neat1v2, enhanced the CSC properties, while knockout of the NEAT1 gene suppressed them. CD44 expression was increased by the overexpression of Neat1v1 and abrogated by NEAT1 knockout. The overexpression of NEAT1v1 restored the CSC properties and CD44 expression in NEAT1-knockout cells. NEAT1v1 expression in HCC tissues was correlated with poor prognosis and CD44 expression. These results suggest that NEAT1v1 is required for CD44 expression. To our surprise, NEAT1v1 also restored the CSC properties even in CD44-deficient cells, suggesting that NEAT1v1 maintains the properties of CSCs in a CD44-independent manner. View Full-Text
Keywords: cancer stem cells; NEAT1; hepatocellular carcinoma; CD44; spheroid cancer stem cells; NEAT1; hepatocellular carcinoma; CD44; spheroid
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MDPI and ACS Style

Koyama, S.; Tsuchiya, H.; Amisaki, M.; Sakaguchi, H.; Honjo, S.; Fujiwara, Y.; Shiota, G. NEAT1 is Required for the Expression of the Liver Cancer Stem Cell Marker CD44. Int. J. Mol. Sci. 2020, 21, 1927. https://doi.org/10.3390/ijms21061927

AMA Style

Koyama S, Tsuchiya H, Amisaki M, Sakaguchi H, Honjo S, Fujiwara Y, Shiota G. NEAT1 is Required for the Expression of the Liver Cancer Stem Cell Marker CD44. International Journal of Molecular Sciences. 2020; 21(6):1927. https://doi.org/10.3390/ijms21061927

Chicago/Turabian Style

Koyama, Shigemi, Hiroyuki Tsuchiya, Masataka Amisaki, Hiromi Sakaguchi, Soichiro Honjo, Yoshiyuki Fujiwara, and Goshi Shiota. 2020. "NEAT1 is Required for the Expression of the Liver Cancer Stem Cell Marker CD44" International Journal of Molecular Sciences 21, no. 6: 1927. https://doi.org/10.3390/ijms21061927

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