Department of Hematology, Xi'an Central Hospital Affiliated to Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Cancer Med. 2020 Jul;9(14):5235-5246. doi: 10.1002/cam4.3046. Epub 2020 May 27.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Numerous analyses have revealed the abnormal expression of long non-coding RNAs (lncRNAs) in HCC cells. This study aims to explore biological functions of lncRNA TMPO-AS1 (TMPO antisense RNA 1) in HCC cell proliferation, apoptosis, invasion and migration.
The gene expression in HCC tissues and cell lines were measured by qRT-PCR. The role of TMPO-AS1 in HCC was confirmed by CCK-8, colony formation, TUNEL, transwell and western blot as well as by in vivo experiments. RNA pull down and luciferase reporter assays were utilized to prove the binding relationship between TMPO-AS1/FOXK1 (forkhead box K1) andmiR-329-3p. Rescue assays elucidated the regulatory effects of TMPO-AS1/miR-329-3p/FOXK1/AKT/mTOR pathway on cellular activities in HCC.
TMPO-AS1was upregulated in HCC tissues and cells and its depletion inhibits HCC cell proliferation, invasion, migration, and EMT process as well as tumor growth. Furthermore, TMPO-AS1 could bind with miR-329-3p, which suppressed HCC cell proliferation. FOXK1 served as the target gene of miR-329-3p and TMPO-AS1 upregulated FOXK1 by sponging miR-329-3p in HCC cells. Additionally, FOXK1 overexpression or miR-329-3p inhibitor neutralized the repressing effects of TMPO-AS1 knockdown on HCC development. Finally, it verified that TMPO-AS1 could regulate AKT/mTOR pathway via FOXK1 to promote HCC.
TMPO-AS1 contributes to HCC progression by sponging miR-329-3p to activate FOXK1-mediated AKT/mTOR signaling pathway.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。大量分析表明 HCC 细胞中长链非编码 RNA（lncRNA）表达异常。本研究旨在探讨 lncRNA TMPO-AS1（TMPO 反义 RNA 1）在 HCC 细胞增殖、凋亡、侵袭和迁移中的生物学功能。
通过 qRT-PCR 测量 HCC 组织和细胞系中的基因表达。通过 CCK-8、集落形成、TUNEL、Transwell 和 Western blot 以及体内实验证实了 TMPO-AS1 在 HCC 中的作用。利用 RNA 下拉和荧光素酶报告基因实验证明了 TMPO-AS1/FOXK1（叉头框 K1）与 miR-329-3p 的结合关系。通过挽救实验阐明了 TMPO-AS1/miR-329-3p/FOXK1/AKT/mTOR 通路对 HCC 细胞活性的调节作用。
TMPO-AS1 在 HCC 组织和细胞中上调，其缺失抑制 HCC 细胞增殖、侵袭、迁移和 EMT 过程以及肿瘤生长。此外，TMPO-AS1 可以与 miR-329-3p 结合，从而抑制 HCC 细胞增殖。FOXK1 是 miR-329-3p 的靶基因，TMPO-AS1 通过在 HCC 细胞中海绵 miR-329-3p 上调 FOXK1。此外，FOXK1 的过表达或 miR-329-3p 抑制剂可中和 TMPO-AS1 敲低对 HCC 发展的抑制作用。最后，验证了 TMPO-AS1 可以通过 FOXK1 调节 AKT/mTOR 通路来促进 HCC。
TMPO-AS1 通过海绵 miR-329-3p 激活 FOXK1 介导的 AKT/mTOR 信号通路促进 HCC 的进展。
