N-Acetyltransferase 10 Enhances Doxorubicin Resistance in Human Hepatocellular Carcinoma Cell Lines by Promoting the Epithelial-to-Mesenchymal Transition

Joint Authors

Chen, Jiang
Liang, Xiao
He, Shilin
Zhang, Xiuming
Jiang, Shi
Bai, Yanfeng
Zhu, Linghua
Ma, Rui

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2019-07-01

Country of Publication

Egypt

No. of Pages

14

Main Subjects

Biology

Abstract EN

Background.

N-Acetyltransferase 10 (NAT10) has been reported to be expressed at high levels in hepatocellular carcinoma (HCC); however, its role in chemoresistance is unclear.

This study is aimed at investigating whether NAT10 regulates the epithelial-mesenchymal transition (EMT) and chemoresistance in HCC.

Methods.

HCC cell lines (Huh-7, Bel-7402, SNU387, and SNU449) were treated with remodelin, an inhibitor of NAT10, or transfected with small inhibitory RNAs (siRNAs) targeting NAT10 or Twist.

The EMT was induced by hypoxia.

The CCK-8 assay was used to quantify cell viability, the EdU incorporation assay to assess cell proliferation.

siRNA knockdown efficiency and epithelial/mesenchymal marker expression were assessed by western blotting.

Results.

Knockdown of NAT10 using siRNA or inhibition of NAT10 using remodelin increased the sensitivity of HCC cell lines to doxorubicin; similar effects were observed in cells transfected with the Twist siRNA.

Inhibition of NAT10 using remodelin also reversed the ability of doxorubicin to induce the EMT in HCC cells.

Furthermore, inhibiting NAT10 reversed the hypoxia-induced EMT.

Finally, we confirmed that combining doxorubicin with remodelin delayed tumor growth and reduced tumor cell proliferation in a mouse xenograft model of HCC.

Conclusions.

NAT10 may contribute to chemoresistance in HCC by regulating the EMT.

The mechanism by which NAT10 regulates the EMT and doxorubicin sensitivity in HCC cells merits further investigation.

American Psychological Association (APA)

Zhang, Xiuming& Chen, Jiang& Jiang, Shi& He, Shilin& Bai, Yanfeng& Zhu, Linghua…[et al.]. 2019. N-Acetyltransferase 10 Enhances Doxorubicin Resistance in Human Hepatocellular Carcinoma Cell Lines by Promoting the Epithelial-to-Mesenchymal Transition. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1205195

Modern Language Association (MLA)

Zhang, Xiuming…[et al.]. N-Acetyltransferase 10 Enhances Doxorubicin Resistance in Human Hepatocellular Carcinoma Cell Lines by Promoting the Epithelial-to-Mesenchymal Transition. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1205195

American Medical Association (AMA)

Zhang, Xiuming& Chen, Jiang& Jiang, Shi& He, Shilin& Bai, Yanfeng& Zhu, Linghua…[et al.]. N-Acetyltransferase 10 Enhances Doxorubicin Resistance in Human Hepatocellular Carcinoma Cell Lines by Promoting the Epithelial-to-Mesenchymal Transition. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1205195

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1205195