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长链非编码RNA-OIS1通过上调MTK-1抑制人乳头瘤病毒阳性而非人乳头瘤病毒阴性的宫颈鳞状细胞癌。

Long non-coding RNA-OIS1 inhibits HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1.

作者信息

Zhou Dan, Wu Fengli, Cui Ying, Wei Fenghua, Meng Qingwei, Lv Qiubo

机构信息

Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China.

出版信息

Oncol Lett. 2019 Mar;17(3):2923-2930. doi: 10.3892/ol.2019.9891. Epub 2019 Jan 4.

Abstract

Long non-coding RNA-oncogene-induced senescence 1 (lncRNA-OIS1) is a novel lncRNA that is involved in oncogene-induced senescence, while its functionality in cervical squamous cell carcinoma is unknown. In the present study, 68 human papillomavirus (HPV)-positive and 22 HPV-negative patients with cervical squamous cell carcinoma were recruited. Additionally, 40 healthy females were employed as healthy controls. Tumor tissues and adjacent healthy tissues were collected from all patients with cervical squamous cell carcinoma, and blood samples were obtained. Expression of OIS1 was detected by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of OIS1 for cervical squamous cell carcinoma. HPV-positive and HPV-negative cervical squamous cell carcinoma and normal cervical cell lines were used, and the effects of OIS1 or mitogen-activated protein kinase kinase kinase 4, (MTK-1) expression vector transfection on the proliferation of cell lines and MTK-1 expression were detected by CCK-8 assay and western blotting, respectively. It was established that a reduction in OIS1 expression level in tumor tissues was apparent only in HPV-positive patients. Serum levels of OIS1 were lower in HPV-positive patients compared with that in HPV-negative patients and healthy controls, and no significant differences were observed between HPV-negative patients and healthy controls. Serum levels of OIS1 were significantly associated with tumor size, but not distant tumor metastasis. OIS1 expression level was lower in HPV-positive cancer cell lines compared with that in HPV-negative cancer cell lines, while no significant differences were observed between HPV-positive and HPV-negative normal cell lines. OIS1 overexpression inhibited and MTK-1 overexpression promoted the proliferation of HPV-positive, but not HPV-negative cancer or normal cell lines. OIS1 transfection also decreased the expression of MTK-1 in HPV-positive cancer cell lines, but not in any of the other cell lines. Therefore, it was concluded that OIS1 inhibited HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1.

摘要

长链非编码RNA-癌基因诱导衰老1(lncRNA-OIS1)是一种新型的长链非编码RNA,参与癌基因诱导的衰老过程,但其在宫颈鳞状细胞癌中的功能尚不清楚。在本研究中,招募了68例人乳头瘤病毒(HPV)阳性和22例HPV阴性的宫颈鳞状细胞癌患者。此外,40名健康女性作为健康对照。收集了所有宫颈鳞状细胞癌患者的肿瘤组织和相邻的健康组织,并采集了血液样本。通过逆转录-定量聚合酶链反应检测OIS1的表达。采用受试者工作特征曲线分析评估OIS1对宫颈鳞状细胞癌的诊断价值。使用HPV阳性和HPV阴性的宫颈鳞状细胞癌以及正常宫颈细胞系,分别通过CCK-8法和蛋白质印迹法检测OIS1或丝裂原活化蛋白激酶激酶激酶4(MTK-1)表达载体转染对细胞系增殖和MTK-1表达的影响。结果表明,仅在HPV阳性患者的肿瘤组织中OIS1表达水平明显降低。与HPV阴性患者和健康对照相比,HPV阳性患者的血清OIS1水平较低,而HPV阴性患者和健康对照之间未观察到显著差异。血清OIS1水平与肿瘤大小显著相关,但与远处肿瘤转移无关。与HPV阴性癌细胞系相比,HPV阳性癌细胞系中OIS1表达水平较低,而HPV阳性和HPV阴性正常细胞系之间未观察到显著差异。OIS1过表达抑制而MTK-1过表达促进HPV阳性而非HPV阴性癌细胞或正常细胞系的增殖。OIS1转染还降低了HPV阳性癌细胞系中MTK-1的表达,但在其他任何细胞系中均未降低。因此,得出结论:OIS1通过上调MTK-1抑制HPV阳性而非HPV阴性的宫颈鳞状细胞癌。

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Cervical Cancer, Version 2.2015.宫颈癌临床实践指南(2015 年版)
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