a Department of Chinese and Western Integrative Medicine and Department of Clinical Laboratory , Beijing University of Chinese Medicine Third Affiliated Hospital , Beijing , China.
b Department of Spine Orthopaedics , Liaocheng Traditional Chinese Medicine hospital , Liaocheng , China.
Cancer Biol Ther. 2019;20(4):461-473. doi: 10.1080/15384047.2018.1529124. Epub 2018 Nov 7.
Gastric cancer (GC) is a serious threat for public health worldwide. Long non-coding RNA (lncRNA) linc00152 has been well reported to be an oncogene and a potential biomarker in multiple cancers including GC. However, the molecular mechanisms of linc00152 in GC development need to be further investigated.
RT-qPCR assay was employed to detect the levels of linc00152, microRNA-193b-3p (miR-193b-3p) and ETS1 mRNA. ETS1 protein level was measured by western blot assay. Cell proliferative, migratory and invasive capacities were assessed by colony formation together with CCK-8 assays, transwell migration and invasion assays, respectively. Bioinformatics analyses and luciferase reporter assay were used to explore whether miR-193b-3p could interact with linc00152 or ETS1 3'UTR. The roles and molecular basis of linc00152 silence on the growth of GC xenograft tumors were tested in vivo.
Linc00152 expression was notably upregulated in GC tissues and cells. The proliferative, migratory and invasive abilities of GC cells were weakened by linc00152 depletion, miR-193b-3p overexpression or ETS1 knockdown. Linc00152 upregulation inhibited miR-193b-3p expression by direct interaction and abolished miR-193b-3p-mediated anti-proliferation, anti-migration and anti-invasion effects in GC cells. ETS1 was a target of miR-193b-3p and linc00152 could promote ETS1 expression by downregulating miR-193b-3p. In vivo experiments further validated that linc00152 knockdown inhibited the growth of GC xenograft tumors by upregulating miR-193b-3p and downregulating ETS1.
Knockdown of linc00152 inhibited GC progression by sequestering miR-193b-3p from ETS1 in vitro and in vivo, elucidating a novel molecular mechanism of linc00152 in promoting GC carcinogenesis.
胃癌（GC）是全球公共健康的严重威胁。长链非编码 RNA（lncRNA）linc00152 已被充分报道为多种癌症（包括 GC）中的癌基因和潜在生物标志物。然而，linc00152 在 GC 发展中的分子机制仍需进一步研究。
采用 RT-qPCR 法检测 linc00152、微小 RNA-193b-3p（miR-193b-3p）和 ETS1 mRNA 的水平。采用 Western blot 法测定 ETS1 蛋白水平。通过集落形成和 CCK-8 检测、Transwell 迁移和侵袭检测分别评估细胞增殖、迁移和侵袭能力。采用生物信息学分析和荧光素酶报告基因检测探讨 miR-193b-3p 是否与 linc00152 或 ETS1 3'UTR 相互作用。体内实验检测 linc00152 沉默对 GC 异种移植肿瘤生长的作用及分子机制。
GC 组织和细胞中 linc00152 表达明显上调。linc00152 耗竭、miR-193b-3p 过表达或 ETS1 敲低均减弱 GC 细胞的增殖、迁移和侵袭能力。linc00152 上调通过直接相互作用抑制 miR-193b-3p 的表达，并消除 miR-193b-3p 介导的 GC 细胞增殖、迁移和侵袭抑制作用。ETS1 是 miR-193b-3p 的靶基因，linc00152 通过下调 miR-193b-3p 促进 ETS1 表达。体内实验进一步验证了 linc00152 敲低通过上调 miR-193b-3p 和下调 ETS1 抑制 GC 异种移植肿瘤的生长。
体外和体内实验均表明，linc00152 敲低通过将 miR-193b-3p 从 ETS1 上隔离来抑制 GC 进展，揭示了 linc00152 促进 GC 癌变的新分子机制。
