Ren Kaiming, Xu Ran, Huang Jingshan, Zhao Jungang, Shi Wenjun
Department of Thoracic Surgery, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping Area, Shenyang, 110004, Liaoning, China.
Cancer Chemother Pharmacol. 2017 Aug;80(2):243-250. doi: 10.1007/s00280-017-3356-z. Epub 2017 Jun 9.
Lung cancer, with the highest morbidity and second highest death rates, is one of the most common cancers in both males and females worldwide. Lung adenocarcinoma (LAD) is the main lung cancer class. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) gene is an lncRNA which had been reported high-expression in colorectal cancer. In this study, the expression of KCNQ1OT1 was confirmed to be highly expressed in LAD tissues and cells contrast to control tissues and cells, and high KCNQ1OT1 expression correlated to malignant behaviors of LAD, including big tumor size, poor differentiation, positive lymphatic metastasis and high TNM stages. The transfection of si-KCNQ1OT1 could effectually knockdown the expression of KCNQ1OT1 in A549 and A549/PA cells. The KCNQ1OT1 knockdown depressed the proliferation and invasion of A549 cells, and advanced cellular apoptosis of A549 cells. The expression of KCNQ1OT1 in LAD patients insensitive to paclitaxel was much higher than that in LAD patients sensitive to paclitaxel; the KCNQ1OT1 expression in A549/PA cells was also much higher than that in control A549 cells. The half maximal inhibitory concentration (IC50) of paclitaxel in A549/PA cells was depressed by KCNQ1OT1 knockdown, chemoresistance of A549/PA cells was inhibited significantly. KCNQ1OT1 knockdown also depressed the expression of multidrug resistance 1 (MDR1) protein in A549/PA cells. In summary, lncRNA KCNQ1OT1 was highly expressed in LAD and functioned as a potential oncogene to inhibit malignancy and chemoresistance of LAD cells, which might be a novel potential therapeutic target for LAD.
肺癌是全球男性和女性中最常见的癌症之一，其发病率最高，死亡率次之。肺腺癌（LAD）是主要的肺癌类型。KCNQ1反义链/反义转录本1（KCNQ1OT1）基因是一种lncRNA，已报道其在结直肠癌中高表达。在本研究中，与对照组织和细胞相比，KCNQ1OT1在LAD组织和细胞中被证实高表达，且KCNQ1OT1高表达与LAD的恶性行为相关，包括肿瘤体积大、分化差、淋巴转移阳性和TNM分期高。si-KCNQ1OT1转染可有效敲低A549和A549/PA细胞中KCNQ1OT1的表达。KCNQ1OT1敲低抑制了A549细胞的增殖和侵袭，并促进了A549细胞的凋亡。对紫杉醇不敏感的LAD患者中KCNQ1OT1的表达远高于对紫杉醇敏感的LAD患者；A549/PA细胞中KCNQ1OT1的表达也远高于对照A549细胞。KCNQ1OT1敲低降低了A549/PA细胞中紫杉醇的半数最大抑制浓度（IC50），显著抑制了A549/PA细胞的化疗耐药性。KCNQ1OT1敲低还降低了A549/PA细胞中多药耐药蛋白1（MDR1）的表达。总之，lncRNA KCNQ1OT1在LAD中高表达，并作为一种潜在的癌基因发挥作用，抑制LAD细胞的恶性和化疗耐药性，这可能是LAD的一个新的潜在治疗靶点。
