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Theranostics 2020; 10(13):5671-5686. doi:10.7150/thno.42539 This issue Cite

Research Paper

SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma

Hongfa Xu1*, Hao Wang1*, Wei Zhao1*, Sirui Fu1, Yong Li1, Wenjun Ni2, Yongjie Xin1, Wei Li1, Chenzi Yang1, Yanyan Bai3, Meixiao Zhan1✉, Ligong Lu1✉

1. Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, 519000, China.
2. Department of urinary surgery, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, 519000, China.
3. School of Stomatology, Changsha Medical University, Changsha City, Hunan, 410219, China.
*Hongfa Xu, Hao Wang and Wei Zhao contributed equally to this work.

✉ Corresponding authors: Ligong Lu (luligong1969edu.cn) and Meixiao Zhan (zhanmeixiao1987com)

Citation:
Xu H, Wang H, Zhao W, Fu S, Li Y, Ni W, Xin Y, Li W, Yang C, Bai Y, Zhan M, Lu L. SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma. Theranostics 2020; 10(13):5671-5686. doi:10.7150/thno.42539. https://www.thno.org/v10p5671.htm
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Abstract

Graphic abstract

Rationale: Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide. Methyltransferase-like 3 (Mettl3), an RNA N6-methyladenosine (m6A) methyltransferase, has been shown to act as an oncogene in several human cancers. However, the regulatory role of posttranslational modifications of Mettl3 in liver cancer remains elusive.

Methods: SUMOylation was analyzed using immunoprecipitation and western blot assays. In vitro and in vivo biological functions were examined using MTS, colony formation, wound healing, transwell, apoptosis, and viability assays and the BALB/c nude mouse model, respectively. Immunohistochemistry was conducted to evaluate the prognostic value of Mettl3 expression in HCC. The regulatory mechanism of Mettl3 in HCC was investigated by m6A dot blot, immunofluorescence, dual luciferase reporter, protein stability, and RNA stability assays.

Results: Mettl3 was found to be SUMOylated by a small ubiquitin-like modifier SUMO1. Further, SUMOylation of Mettl3 was increased upon mitogen stimulation, which correlated with UBC9 upregulation, and was positively correlated with high metastatic potential of liver cancer. Finally, SUMOylation of Mettl3 was found to regulate HCC progression via controlling Snail mRNA homeostasis in an m6A methyltransferase activity-dependent manner.

Conclusions: This study revealed a novel mechanism of SUMOylated Mettl3-mediated Snail mRNA homeostasis, identifying the UBC9/SUMOylated Mettl3/Snail axis as a novel mediator of the SUMO pathway involved in HCC progression.

Keywords: Hepatocellular carcinoma, N6-methyladenosine, SUMOylations, Mettl3, Snail

Citation styles

APA
Xu, H., Wang, H., Zhao, W., Fu, S., Li, Y., Ni, W., Xin, Y., Li, W., Yang, C., Bai, Y., Zhan, M., Lu, L. (2020). SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma. Theranostics, 10(13), 5671-5686. https://doi.org/10.7150/thno.42539.

ACS
Xu, H.; Wang, H.; Zhao, W.; Fu, S.; Li, Y.; Ni, W.; Xin, Y.; Li, W.; Yang, C.; Bai, Y.; Zhan, M.; Lu, L. SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma. Theranostics 2020, 10 (13), 5671-5686. DOI: 10.7150/thno.42539.

NLM
Xu H, Wang H, Zhao W, Fu S, Li Y, Ni W, Xin Y, Li W, Yang C, Bai Y, Zhan M, Lu L. SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma. Theranostics 2020; 10(13):5671-5686. doi:10.7150/thno.42539. https://www.thno.org/v10p5671.htm

CSE
Xu H, Wang H, Zhao W, Fu S, Li Y, Ni W, Xin Y, Li W, Yang C, Bai Y, Zhan M, Lu L. 2020. SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma. Theranostics. 10(13):5671-5686.

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