The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang 310014, China.
Int J Biol Sci. 2020 Jun 5;16(13):2296-2305. doi: 10.7150/ijbs.45457. eCollection 2020.
Hepatocellular carcinoma (HCC), one of the main causes of cancer-related deaths globally, is characterized by rapid growth and high invasiveness. Accumulating evidence demonstrates that long noncoding RNAs (lncRNAs) play critical roles in the growth and metastasis of HCC. Recently, lncRNA LINC01123 has been found to contribute to cell proliferation and aerobic glycolysis in lung cancer. However, the function of LINC01123 in HCC, as well as the underlying mechanism of its action, remain unclear. Here, we found that the expression of LINC01123 was clearly upregulated in HCC tissues compared to nontumor tissues. Furthermore, expression of LINC01123 in HCC cells was significantly higher than in LO2 cells. Importantly, the upregulated level of LINC01123 was related to unfavorable clinical features and poor prognosis of HCC. Next, we demonstrated that LINC01123 knockdown suppressed the proliferation, migration and invasion of HCC cells . Depletion of LINC01123 inhibited HCC xenograft growth . Conversely, ectopic expression of LINC01123 facilitated HCC cell proliferation and invasion. Mechanistically, LINC01123 acted as a molecular sponge for miR-34a-5p in HCC cells. Tuftelin1 (TUFT1) was identified as the target gene of miR-34a-5p. LINC01123 positively regulated TUFT1 level by targeting of miR-34a-5p in HCC cells. Notably, TUFT1 restoration can abolish miR-34a-5p-induced inhibitory effects on HCC cell proliferation, migration and invasion. In conclusion, LINC01123 was overexpressed in HCC and accelerated cancer cell proliferation and invasion by regulating the miR-34a-5p/TUFT1 axis.
肝细胞癌 (HCC) 是全球癌症相关死亡的主要原因之一，其特点是生长迅速且具有高度侵袭性。越来越多的证据表明，长链非编码 RNA (lncRNA) 在 HCC 的生长和转移中发挥着关键作用。最近，lncRNA LINC01123 被发现有助于肺癌细胞的增殖和有氧糖酵解。然而，LINC01123 在 HCC 中的功能以及其作用的潜在机制尚不清楚。在这里，我们发现 LINC01123 的表达在 HCC 组织中明显高于非肿瘤组织。此外，LINC01123 在 HCC 细胞中的表达明显高于 LO2 细胞。重要的是，LINC01123 的上调水平与 HCC 的不良临床特征和预后不良有关。接下来，我们证明了 LINC01123 的敲低抑制了 HCC 细胞的增殖、迁移和侵袭。LINC01123 的耗竭抑制了 HCC 异种移植物的生长。相反，LINC01123 的异位表达促进了 HCC 细胞的增殖和侵袭。机制上，LINC01123 在 HCC 细胞中作为 miR-34a-5p 的分子海绵起作用。Tuftelin1 (TUFT1) 被鉴定为 miR-34a-5p 的靶基因。LINC01123 通过靶向 miR-34a-5p 正向调节 HCC 细胞中的 TUFT1 水平。值得注意的是，TUFT1 的恢复可以消除 miR-34a-5p 对 HCC 细胞增殖、迁移和侵袭的抑制作用。总之，LINC01123 在 HCC 中过表达，并通过调节 miR-34a-5p/TUFT1 轴加速癌细胞增殖和侵袭。
