Department of Otorhinolaryngology and Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).
Med Sci Monit. 2018 Jul 3;24:4592-4601. doi: 10.12659/MSM.908652.
BACKGROUND The aim of this study was to explore the potential effects of long noncoding RNA (lncRNA) LINC003121 on thyroid cancer (TC) cell proliferation and invasion and to explore their possible mechanisms with the involvement of the PI3K/Akt signaling pathway. MATERIAL AND METHODS We enrolled 211 thyroid cancer tissues and 70 adjacent normal tissues in this study. TC cell lines K1, SW579, and 8505C and the human thyroid follicular cell line Nthy-ori3-1 were selected and assigned into blank, control vectors, LINC00312 vectors, si-control, and si-LINC00312 groups. Quantitative real-time PCR was used to determine the levels of LINC003121 and Western blotting was used to detect the protein expression of MMP-9, PI3K, t-Akt, and p-Akt. Cell proliferation was assessed by CCK8 assay and EdU incorporation assay, and cell invasion was assessed by Transwell assay. RESULTS The expression of LINC00312 was significantly decreased in TC tissues and cell lines. In an in vitro experiment, si-LINC00312 significantly promoted the invasion and proliferation of TC cells. Conversely, overexpression of LINC00312 decreased cell proliferation and invasion in vitro, and decreased tumorigenicity in TC xenograft models in nude mice. LINC00312-mediated tumor suppression in TC cells may occur via suppression of activation of the PI3K/Akt signaling pathway and expression of MMP-9, and the role of MMP-9 expression induced by overexpressed LINC00312 or si-LINC00312 could be weakened by LY294002 (PI3K inhibitor). CONCLUSIONS LINC00312 can act as a tumor-suppressor in TC by attenuating the PI3K/Akt signaling pathway, and LINC00312 could be a novel diagnosis biomarker and a promising therapeutic target for TC patients.
本研究旨在探讨长链非编码 RNA（lncRNA）LINC003121 对甲状腺癌（TC）细胞增殖和侵袭的潜在影响，并探讨其可能通过 PI3K/Akt 信号通路发挥作用的机制。
本研究纳入 211 例甲状腺癌组织和 70 例癌旁正常组织。选择 TC 细胞系 K1、SW579 和 8505C 以及人甲状腺滤泡细胞系 Nthy-ori3-1，并分为空白组、对照组载体、LINC00312 载体、si-control 和 si-LINC00312 组。采用实时定量 PCR 检测 LINC003121 的水平，采用 Western blot 检测 MMP-9、PI3K、t-Akt 和 p-Akt 的蛋白表达。采用 CCK8 法和 EdU 掺入法检测细胞增殖，采用 Transwell 法检测细胞侵袭。
LINC00312 在 TC 组织和细胞系中的表达显著降低。在体外实验中，si-LINC00312 显著促进 TC 细胞的侵袭和增殖。相反，过表达 LINC00312 可降低 TC 细胞的体外增殖和侵袭，并降低裸鼠 TC 移植瘤模型中的肿瘤生成能力。LINC00312 对 TC 细胞的肿瘤抑制作用可能是通过抑制 PI3K/Akt 信号通路的激活和 MMP-9 的表达来实现的，而过表达 LINC00312 或 si-LINC00312 诱导的 MMP-9 表达作用可以被 LY294002（PI3K 抑制剂）削弱。
LINC00312 可通过抑制 PI3K/Akt 信号通路在 TC 中发挥肿瘤抑制作用，LINC00312 可能成为 TC 患者的新型诊断生物标志物和有前途的治疗靶点。
