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

DDX11-AS1 TAF1 TOP2A esophageal cancer paclitaxel resistance

Journal

American journal of cancer research
ISSN: 2156-6976
Titre abrégé: Am J Cancer Res
Pays: United States
ID NLM: 101549944

Informations de publication

Date de publication:
2019
Historique:
received: 30 04 2019
accepted: 18 08 2019
entrez: 14 11 2019
pubmed: 14 11 2019
medline: 14 11 2019
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31720085
pmc: PMC6834486

Types de publication

Journal Article

Langues

eng

Pagination

2233-2248

Informations de copyright

AJCR Copyright © 2019.

Déclaration de conflit d'intérêts

None.

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Auteurs

Shuyao Zhang (S)

Department of Pharmacy, Guangzhou Red Cross Hospital Affiliated of Ji-Nan University Medical College Guangzhou 510220, Guangdong Province, P. R. China.
Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Hong Jiang (H)

Department of Nursing, Guangzhou Red Cross Hospital Affiliated of Ji-Nan University Medical College Guangzhou 510220, Guangdong Province, P. R. China.

Zhe Xu (Z)

Department of Urology, Cancer Hospital of Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Yi Jiang (Y)

Department of Digestive Oncology, Cancer Hospital of Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Yuqi She (Y)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Xiaoting Huang (X)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Shanna Feng (S)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Wanying Chen (W)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Shuang Chen (S)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Yun Chen (Y)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Guodong Qiu (G)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.

Shilong Zhong (S)

Clinical Pharmacy Research Center, Shantou University Medical College Shantou 515031, Guangdong Province, P. R. China.
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.

Classifications MeSH