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食管鳞状细胞癌中circ_0004365与顺铂耐药性之间的关联

Association between circ_0004365 and cisplatin resistance in esophageal squamous cell carcinoma.

作者信息

Yamada Moyuru, Tanaka Koji, Yamamoto Kenichi, Matsumoto Hisatake, Yamasaki Makoto, Yamashita Kotaro, Makino Tomoki, Saito Takuro, Yamamoto Kazuyoshi, Takahashi Tsuyoshi, Kurokawa Yukinori, Nakajima Kiyokazu, Okada Yukinori, Eguchi Hidetoshi, Doki Yuichiro

机构信息

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

出版信息

Oncol Lett. 2023 Sep 18;26(5):467. doi: 10.3892/ol.2023.14054. eCollection 2023 Nov.

Abstract

Cisplatin is one of the most predominant drugs for the chemotherapy of esophageal squamous cell carcinoma (ESCC); however, the underlying resistance mechanisms are still almost unknown. The present study performed RNA sequencing of human circular RNA (circRNA) in TE11 cells and cisplatin-resistant TE11 cells (TE11R). The expression profiles determined using CIRCexplorer2 revealed that the expression of circ_0004365, mapped on the Semaphorin 3C gene, was significantly greater in TE11R compared with in TE11. In reverse transcription-quantitative PCR, circ_0004365 expression was observed in human ESCC and non-tumor tissues and was significantly upregulated in ESCC tumor tissues after chemotherapy. Circ_0004365 expression was significantly upregulated in patients with poor pathological response (P=0.02). Furthermore, patients with advanced pT stage showed an upregulation in circ_0004365 expression after chemotherapy (P=0.02). The MTT assay revealed that knockdown of circ_0003465 in TE11 significantly decreased resistance to cisplatin. In conclusion, the present study suggested that circ_0004365 was associated with cisplatin resistance in ESCC and can be used as both a novel biomarker and a therapeutic target.

摘要

顺铂是食管鳞状细胞癌(ESCC)化疗中最主要的药物之一;然而,其潜在的耐药机制仍几乎未知。本研究对人环状RNA(circRNA)在TE11细胞和顺铂耐药的TE11细胞(TE11R)中进行了RNA测序。使用CIRCexplorer2确定的表达谱显示,定位于信号素3C基因上的circ_0004365在TE11R中的表达明显高于TE11。在逆转录定量PCR中,在人ESCC和非肿瘤组织中观察到circ_0004365的表达,且化疗后ESCC肿瘤组织中其表达明显上调。病理反应差的患者中circ_0004365表达明显上调(P=0.02)。此外,pT分期较晚的患者化疗后circ_0004365表达上调(P=0.02)。MTT试验显示,在TE11中敲低circ_0003465可显著降低对顺铂的耐药性。总之,本研究表明circ_0004365与ESCC中的顺铂耐药相关,可作为一种新型生物标志物和治疗靶点。

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