Role of DDX53 in taxol-resistance of cervix cancer cells in vitro

Su Yeon Park; Won Jin Kim; Jae Hwan Byun; Jae Jun Lee; Dooil Jeoung; Sung Taek Park; Youngmi Kim

doi:10.1016/j.bbrc.2018.10.145

Role of DDX53 in taxol-resistance of cervix cancer cells in vitro

Biochem Biophys Res Commun. 2018 Nov 30;506(3):641-647. doi: 10.1016/j.bbrc.2018.10.145. Epub 2018 Oct 26.

Authors

Su Yeon Park¹, Won Jin Kim², Jae Hwan Byun³, Jae Jun Lee⁴, Dooil Jeoung³, Sung Taek Park⁵, Youngmi Kim⁶

Affiliations

¹ Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul, South Korea.
² Department of Anesthesiology and Pain Medicine, College of Medicine, Hallym University, Chuncheon, South Korea.
³ Department of Biochemistry, Kangwon National University, Chuncheon, South Korea.
⁴ Institute of New Frontier Research, College of Medicine, Hallym University, Chuncheon, South Korea; Department of Anesthesiology and Pain Medicine, College of Medicine, Hallym University, Chuncheon, South Korea.
⁵ Institute of New Frontier Research, College of Medicine, Hallym University, Chuncheon, South Korea; Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul, South Korea. Electronic address: parkst96@hallym.ac.kr.
⁶ Institute of New Frontier Research, College of Medicine, Hallym University, Chuncheon, South Korea. Electronic address: kym8389@hallym.ac.kr.

PMID: 30454700
DOI: 10.1016/j.bbrc.2018.10.145

Abstract

Cancer/Testis antigen DDX53 shows high expression level in various tumors and is involved in anti-cancer drug resistance. However, the functional study of DDX53 in cervix cancer remains unknown. In this study, the role of DDX53 in taxol-resistance of cervix cancer cells was investigated. In taxol-resistant Hela^TR cells, DDX53 was significantly increased as compared to the parental HeLa cells. Hela^TR cells also showed upregulation of multidrug resistant gene MDR1, invasive characteristics and decreased apoptosis. In addition, increased autophagy level was observed in Hela^TR cells. Overexpression of DDX53 in HeLa and SiHa markedly led to greater resistance to taxol and cisplatin, whereas knockdown of DDX53 in Hela^TR cells restored sensitivity, demonstrating that DDX53 regulated taxol resistance in cervix cancer cells. DDX53 overexpression in HeLa and SiHa cells enhanced invasion, migration and anchorage independent growth, DDX53 knockdown showed inverse effects in HeLa^TR cells. When DDX53 expression was suppressed by siRNA, autophagic flux and drug resistance of Hela^TR cells were decreased. In addition, DDX53 was upregulated in cervix cancer tissues from patient with a glassy cell carcinoma of cervix. Taken together, these results suggest that DDX53 plays a critical role in taxol-resistance by activating autophagy and a potential therapeutic target for the treatment of taxol-resistant cervix cancer.

Keywords: Autophagy; Cervix cancer; DDX53; Drug-resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy / drug effects
Autophagy / genetics
DEAD-box RNA Helicases / genetics
DEAD-box RNA Helicases / metabolism*
Drug Resistance, Neoplasm / drug effects*
Drug Resistance, Neoplasm / genetics
Female
Gene Expression Regulation, Neoplastic / drug effects
Gene Knockdown Techniques
HeLa Cells
Humans
Paclitaxel / pharmacology*
Uterine Cervical Neoplasms / genetics
Uterine Cervical Neoplasms / metabolism*
Uterine Cervical Neoplasms / pathology*

Substances

DDX53 protein, human
DEAD-box RNA Helicases
Paclitaxel