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Abstract

Knockdown of Methyltransferase-Like 3 in the Prevention of Malignant Progression of Colorectal Cancer by Downregulating circLMNB1

Author(s): C. P. He, Y. J. Yu, Rui Zhou, P. Ruan, C. Huang, P. B. Wu and Tao Yao*
Department of Gastroenterology, 1Department of Neurology, Renmin Hospital of Wuhan University, Wuchang, Wuhan, Hubei 430060, China

Correspondence Address:
Tao Yao, Department of Gastroenterology, 1Department of Neurology, Renmin Hospital of Wuhan University, Wuchang, Wuhan, Hubei 430060, China, E-mail: yaotao@whu.edu.cn


Circular RNA is crucial for the development of multiple malignant tumors including colorectal cancer. Circular RNA lamin B1 has recently been verified to accelerate colorectal cancer progression. However, it is not clear whether circular RNA lamin B1 can be regulated by the main methylase (methyltransferaselike 3) in colorectal cancer. This study was to explore the mechanism of methyltransferase-like 3-mediated epigenetic reactivation of circular RNA lamin B1 in colorectal cancer. We first analyzed the expression and correlation between methyltransferase-like 3 and circular RNA lamin B1 in colorectal cancer tissues, and then assessed the effects of methyltransferase-like 3 and circular RNA lamin B1 on the malignant properties of colorectal cancer cells by conducting loss-of-function and restoration studies. We also examined the growth and pathological structures in colorectal cancer xenograft tumors, as well as the levels of methyltransferase-like 3, circular RNA lamin B1 and caspase 3 expression in colorectal cancer xenograft tumors by reverse transcription-quantitative polymerase chain reaction, western blotting, hematoxylin and eosin staining and immunohistochemistry. Our results showed that the levels of circular RNA lamin B1 and methyltransferase-like 3 expressions were elevated and positively correlated in colorectal cancer tissues. Functionally, methyltransferase-like 3 silencing could prevent colorectal cancer cell proliferation, migration and invasion, and facilitate apoptosis in colorectal cancer cells by downregulating circular RNA lamin B1. Moreover, we found that knockdown of methyltransferase-like 3 could prevent tumor growth and disrupt the histological structure of colorectal cancer xenograft tumors by reducing circular RNA lamin B1 expression. Our data confirmed that methyltransferase-like 3 knockdown could attenuate the development of colorectal cancer cells by lowering circular RNA lamin B1 expression. This suggests circular RNA lamin B1 as a novel oncogene in colorectal cancer, which could be regulated by methyltransferaselike 3. Methyltransferase-like 3 silencing and circular RNA lamin B1 might be of great significance in colorectal cancer therapy.

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