Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, PR China.
Hunan Cancer Hospital, The Affiliated Tumor Hospital of Xiangya Medical College, Central South University, Changsha, 410008, PR China.
Cell Death Dis. 2019 Jul 11;10(7):533. doi: 10.1038/s41419-019-1740-9.
Lung cancer is the leading cause of cancer-related mortality worldwide. Recently, accumulating data indicate that long noncoding RNAs (LncRNAs) function as novel crucial regulators of diverse biological processes, including proliferation and metastasis, in tumorigenesis. Lnc NONHSAT081507.1 (LINC81507) is associated with lung adenocarcinoma. However, its pathological role in non-small cell lung cancer (NSCLC) remains unknown. In our study we investigated the role of LINC81507 in NSCLC. The expression of LINC81507 was analyzed in 105 paired NSCLC tumor specimens and paired adjacent non-tumorous tissues from NSCLC patients by real-time quantitative PCR (RT-qPCR). Gain- and loss-of-function experiments were conducted to investigate the functions of LINC81507, miR-199b-5p and CAV1. Reduced expression of LINC81507 resulted in cell growth, proliferation, migration and epithelial-mesenchymal transition (EMT) in NSCLC cells, whereas ectopic overexpression of LINC81507 resulted in the opposite effects both in vitro and in vivo. Nuclear and Cytoplasmic fractionation assays showed LINC81507 mainly resided in cytoplasm. Bioinformatics analysis and dual-luciferase assays revealed that miR-199b-5p was a direct target of LINC81507 through binding Ago2. Mechanistic analysis demonstrated that miR-199b-5p specifically targeted the Caveolin1 (CAV1) gene, and LINC81507 inactivated the STAT3 pathway in a CAV1-dependent manner. Taken together, LINC81507 is decreased in NSCLC and functions as a sponge to miR-199b-5p to regulate CAV1/STAT3 pathway, which suggests that LINC81507 serve as a tumor suppressor and potential therapeutic target and biomarker for metastasis and prognosis in NSCLC.
肺癌是全球癌症相关死亡的主要原因。最近，越来越多的数据表明，长非编码 RNA（LncRNAs）作为肿瘤发生过程中多种生物过程（包括增殖和转移）的新型关键调节因子发挥作用。LncNONHSAT081507.1（LINC81507）与肺腺癌有关。然而，其在非小细胞肺癌（NSCLC）中的病理作用尚不清楚。在我们的研究中，我们研究了 LINC81507 在 NSCLC 中的作用。通过实时定量 PCR（RT-qPCR）分析 105 对 NSCLC 肿瘤标本和来自 NSCLC 患者的配对相邻非肿瘤组织中的 LINC81507 表达。进行了增益和功能丧失实验，以研究 LINC81507、miR-199b-5p 和 CAV1 的功能。在 NSCLC 细胞中，LINC81507 表达降低导致细胞生长、增殖、迁移和上皮-间充质转化（EMT），而 LINC81507 的异位过表达在体外和体内均产生相反的效果。核和细胞质分馏测定表明 LINC81507 主要位于细胞质中。生物信息学分析和双荧光素酶报告基因测定显示，miR-199b-5p 通过结合 Ago2 是 LINC81507 的直接靶标。机制分析表明，miR-199b-5p 特异性靶向 Cavin1（CAV1）基因，LINC81507 通过 CAV1 依赖性方式使 STAT3 通路失活。总之，LINC81507 在 NSCLC 中减少，作为 miR-199b-5p 的海绵来调节 CAV1/STAT3 通路，这表明 LINC81507 作为肿瘤抑制因子和潜在的治疗靶点和生物标志物，用于 NSCLC 的转移和预后。
