Department of Respiratory Medicine, First Hospital of Jilin University, Changchun, China.
Eur Rev Med Pharmacol Sci. 2018 Feb;22(4):1020-1027. doi: 10.26355/eurrev_201802_14384.
Lung cancer is one of the most common malignancies worldwide, the morbidity and mortality of which have been on rising in recent years. Moreover, lncRNAs have been implicated in the development of various cancers, as well as cancer treatment and prognosis. In this study, long non-coding RNA (lncRNA) MEG3, an identified tumor suppressor, was explored for its role in the chemotherapy of lung cancer.
All cases were divided into (I+II) group and (III+IV) group according to different stages of tumor node metastasis (TNM), and were divided into sensitive group and insensitive group according to chemotherapy sensitivity. A549 and H292 cells were selected as the resistant cell and non-resistant lung cancer cells. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to detect the expression of MEG3. After transfection with overexpression plasmid pcDNA-MEG3 or/and different concentrations of vincristine, cell viability and proliferation were measured by cell counting kit-8 (CCK-8) assay and plate cloning assay, respectively. Western blotting was used to analyze the expressions of autophagy-related proteins.
In vivo, lncRNA MEG3 was significantly lower in III+IV group and insensitive group than that in I+II group and sensitive group. In vitro, MEG3 expression in resistant cells was significantly lower than that in non-resistant cells. Overexpression of MEG3 significant inhibited the viability and proliferation of both resistant and non-resistant lung cancer cells. Western blot results showed that autophagy level was higher in resistant cells than that in non-resistant cells, while overexpression of MEG3 significantly reduced the expression of autophagy-related proteins. CCK-8 results also indicated that the cell viability was negatively correlated with the dose of vincristine, while the viability of drug-resistant cells was higher than that of non-drug resistant cells after the treatment of vincristine. The vitality of both cells decreased in a concentration-dependent manner after combined treatment with vincristine and MEG3.
Our data indicated that lncRNA MEG3 showed a low expression in chemotherapy-sensitive lung cancer tissues, and overexpression of lncRNA MEG3 attenuated autophagy level, thus increasing the sensitivity of vincristine in chemotherapy of lung cancer.
肺癌是全球最常见的恶性肿瘤之一，近年来其发病率和死亡率呈上升趋势。此外，长链非编码 RNA（lncRNA）已被证实参与多种癌症的发生、发展以及癌症的治疗和预后。本研究旨在探讨长链非编码 RNA（lncRNA）MEG3 在肺癌化疗中的作用，MEG3 是一种已鉴定的肿瘤抑制因子。
根据肿瘤淋巴结转移（TNM）分期不同，将所有病例分为（I+II）组和（III+IV）组，根据化疗敏感性分为敏感组和不敏感组。选择 A549 和 H292 细胞作为耐药细胞和非耐药肺癌细胞。采用实时定量逆转录聚合酶链反应（qRT-PCR）检测 MEG3 的表达。转染过表达质粒 pcDNA-MEG3 及不同浓度长春新碱后，通过细胞计数试剂盒（CCK-8）法和平板克隆实验分别检测细胞活力和增殖。采用 Western blot 分析自噬相关蛋白的表达。
体内实验结果显示，III+IV 期和不敏感组的 lncRNA MEG3 表达明显低于 I+II 期和敏感组。体外实验结果显示，耐药细胞中 MEG3 的表达明显低于非耐药细胞。过表达 MEG3 显著抑制耐药和非耐药肺癌细胞的活力和增殖。Western blot 结果显示，耐药细胞中的自噬水平高于非耐药细胞，而过表达 MEG3 显著降低了自噬相关蛋白的表达。CCK-8 结果也表明，细胞活力与长春新碱的剂量呈负相关，而长春新碱处理后耐药细胞的活力高于非耐药细胞。长春新碱和 MEG3 联合处理后，两种细胞的活力均呈浓度依赖性下降。
本研究数据表明，lncRNA MEG3 在化疗敏感的肺癌组织中表达较低，过表达 lncRNA MEG3 可降低自噬水平，从而提高长春新碱在肺癌化疗中的敏感性。
