CTCF 诱导的 LINC01207 上调通过 miR-1301-3p/PODXL 轴促进胃癌进展。
CTCF-induced upregulation of LINC01207 promotes gastric cancer progression via miR-1301-3p/PODXL axis.
机构信息
Clinical Medical Research Center, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, 010017, China.
Surgery of Abdominal Tumors, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, 010017, China.
出版信息
Dig Liver Dis. 2021 Apr;53(4):486-495. doi: 10.1016/j.dld.2020.12.006. Epub 2021 Jan 22.
BACKGROUND
Long non coding RNAs (lncRNAs) have been validated to be involved in the complicated biological processes during tumor progression. LINC01207 has been identified as an oncogene in several cancer types. However, the function of LINC01207 and its underlying molecular mechanism in gastric cancer (GC) are poorly understood.
METHODS
The expression level of LINC01207, miR-1301-3p and PODXL mRNA was detected in GC tissues and cells by RT-qPCR. The level of PODXL protein was examined by western blot. Colony formation assay, EdU assay, TUNEL assay, caspase-3 activity test and transwell assays were carried out to analyze the effect of LINC01207 on GC cell proliferation, apoptosis, migration and invasion. The interaction between RNAs was confirmed by luciferase reporter assay, RNA pull-down assay and RIP assay.
RESULTS
LINC01207 was expressed at high level in GC tissues and cells. Silencing of LINC01207 impaired GC cell proliferation, migration and invasion but promoted cell apoptosis. Mechanistically, LINC01207 acted as a ceRNA by sponging miR-1301-3p to upregulate PODXL. Besides, miR-1301-3p silencing or PODXL overexpression could abolish the inhibitory effect of LINC01207 knockdown on GC cell growth and migration. CCCTC-binding factor (CTCF) could transcriptionally activate LINC01207 in GC cells.
CONCLUSIONS
CTCF-induced activation of LINC01207 contributes to GC progression through regulating miR-1301-3p/PODXL axis.
背景
长链非编码 RNA（lncRNAs）已被证实参与肿瘤进展过程中的复杂生物学过程。LINC01207 已被确定为几种癌症类型的癌基因。然而，LINC01207 在胃癌（GC）中的功能及其潜在的分子机制仍知之甚少。
方法
通过 RT-qPCR 检测 GC 组织和细胞中 LINC01207、miR-1301-3p 和 PODXL mRNA 的表达水平。Western blot 检测 PODXL 蛋白水平。通过集落形成实验、EdU 实验、TUNEL 实验、caspase-3 活性检测和 Transwell 实验分析 LINC01207 对 GC 细胞增殖、凋亡、迁移和侵袭的影响。通过荧光素酶报告基因实验、RNA 下拉实验和 RIP 实验证实 RNA 间的相互作用。
结果
LINC01207 在 GC 组织和细胞中高表达。沉默 LINC01207 可抑制 GC 细胞增殖、迁移和侵袭，促进细胞凋亡。机制上，LINC01207 通过海绵 miR-1301-3p 而上调 PODXL，发挥 ceRNA 作用。此外，沉默 miR-1301-3p 或过表达 PODXL 可消除 LINC01207 敲低对 GC 细胞生长和迁移的抑制作用。CCCTC 结合因子（CTCF）可在 GC 细胞中转录激活 LINC01207。
结论
CTCF 诱导的 LINC01207 激活通过调节 miR-1301-3p/PODXL 轴促进 GC 进展。
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