Department of Gastroenterology, the No.1 People's Hospital of Jingmen, 448000, Hubei, China.
Department of Traditional Chinese Medicine, the No.1 People's Hospital of Jingmen, Jingmen, 448000, Hubei, China.
Cell Cycle. 2021 Oct;20(20):2102-2113. doi: 10.1080/15384101.2021.1940627. Epub 2021 Oct 6.
Abundant researches have stated that long noncoding RNAs (lncRNAs) are crucial molecules in intricate progression of various cancers in terms of their influence on cell stemness. However, no research has discussed the role of LINC00460 in the stemness of hepatocellular carcinoma (HCC). RT-qPCR and western blot were utilized to respectively examine the RNA and protein levels. Aldehyde dehydrogenase 1 (ALDH1) assays and sphere formation assay were performed to detect cell stemness property in vitro and in vivo subcutaneous xenograft tumor assay was performed to detect tumor growth. Interaction between RNAs was explored by luciferase reporter assays and RNA pull-down assays. Our results showed that LINC00460 was markedly over-expressed in HCC and silencing LINC00460 impaired cell stemness. Additionally, LINC00460 knockdown curbed proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) and drove apoptosis of HCC cells. Further, LINC00460 bound to miR-503-5p and miR-654-3p to protect t-complex 1 (TCP1) from being inhibited by miR-503-5p/miR-654-3p. Rescue experiments confirmed the effect of LINC00460/miR-503-5p/miR-654-3p/TCP1 on HCC cell stemness. In conclusion, LINC00460 aggravated cell stemness in HCC via targeting miR-503-5p/miR-654-3p and TCP1, suggesting that LINC00460 may work as a potential signature for cell stemness in HCC.[Figure: see text].
大量研究表明，长链非编码 RNA（lncRNA）在各种癌症的复杂进展中是至关重要的分子，因为它们影响细胞干性。然而，没有研究探讨 LINC00460 在肝癌（HCC）干性中的作用。RT-qPCR 和 Western blot 分别用于检测 RNA 和蛋白质水平。醛脱氢酶 1（ALDH1）测定和球体形成测定用于体外检测细胞干性特性，体内皮下异种移植肿瘤测定用于检测肿瘤生长。通过荧光素酶报告测定和 RNA 下拉测定探索 RNA 之间的相互作用。我们的结果表明，LINC00460 在 HCC 中明显过表达，沉默 LINC00460 可损害细胞干性。此外，LINC00460 敲低抑制 HCC 细胞的增殖、迁移、侵袭和上皮间质转化（EMT），并驱动细胞凋亡。进一步，LINC00460 与 miR-503-5p 和 miR-654-3p 结合，以保护 t 复合体 1（TCP1）免受 miR-503-5p/miR-654-3p 的抑制。挽救实验证实了 LINC00460/miR-503-5p/miR-654-3p/TCP1 对 HCC 细胞干性的影响。总之，LINC00460 通过靶向 miR-503-5p/miR-654-3p 和 TCP1 加重 HCC 中的细胞干性，表明 LINC00460 可能作为 HCC 细胞干性的潜在标志物。[图：见正文]。
