The resistance of esophageal cancer cells to paclitaxel can be reduced by the knockdown of long noncoding RNA DDX11-AS1 through TAF1/TOP2A inhibition

Shuyao Zhang; Hong Jiang; Zhe Xu; Yi Jiang; Yuqi She; Xiaoting Huang; Shanna Feng; Wanying Chen; Shuang Chen; Yun Chen; Guodong Qiu; Shilong Zhong

The resistance of esophageal cancer cells to paclitaxel can be reduced by the knockdown of long noncoding RNA DDX11-AS1 through TAF1/TOP2A inhibition

Am J Cancer Res. 2019 Oct 1;9(10):2233-2248. eCollection 2019.

Authors

Shuyao Zhang^{1

2}, Hong Jiang³, Zhe Xu⁴, Yi Jiang⁵, Yuqi She², Xiaoting Huang², Shanna Feng², Wanying Chen², Shuang Chen², Yun Chen², Guodong Qiu², Shilong Zhong^{2

6}

Affiliations

¹ Department of Pharmacy, Guangzhou Red Cross Hospital Affiliated of Ji-Nan University Medical College Guangzhou 510220, Guangdong Province, P. R. China.
² Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.
³ Department of Nursing, Guangzhou Red Cross Hospital Affiliated of Ji-Nan University Medical College Guangzhou 510220, Guangdong Province, P. R. China.
⁴ Department of Urology, Cancer Hospital of Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.
⁵ Department of Digestive Oncology, Cancer Hospital of Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.
⁶ Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080, Guangdong Province, P. R. China.

PMID: 31720085
PMCID: PMC6834486

Abstract

Esophageal cancer (EC) is one of the most common malignancies in the world. The currently used chemotherapeutic drug for the treatment of EC is paclitaxel (PTX), the efficacy of which is affected by the development of drug resistance. The present study aims to define the role of the long noncoding RNA (lncRNA) DDX11-AS1 in the progression of EC with the involvement of PTX-resistant EC cells. First, EC and adjacent normal tissue samples were collected from 82 patients with EC, after which the expression levels of DDX11-AS1, TOP2A and TAF1 were determined. The results showed that DDX11-AS1, TOP2A and TAF1 were highly expressed in EC tissues, and there was a positive correlation between the expression levels of DDX11-AS1 and TOP2A. A PTX-resistant EC cell line was constructed. Next, we evaluated the effects of DDX11-AS1 and TOP2A on the resistance of EC cells to PTX, and the regulatory relationships between DDX11-AS1, TOP2A and TAF1 were investigated. DDX11-AS1 could promote TOP2A transcription via TAF1, and the knockdown of TOP2A or DDX11-AS1 could increase the sensitivity of EC cells to PTX. The effect of DDX11-AS1 on the growth of PTX-inhibited tumors was confirmed using a tumor formation assay in nude mice. It was verified that knocking down DDX11-AS1 reduced the expression level of TOP2A and inhibited tumor growth. In conclusion, our findings suggest that DDX11-AS1 knockdown results in reduced resistance of EC cells to PTX by inhibiting TOP2A transcription via TAF1. Therefore, DDX11-AS1 knockdown could be a promising therapeutic strategy for EC.

Keywords: DDX11-AS1; TAF1; TOP2A; esophageal cancer; paclitaxel; resistance.