Department of Hepatobiliary Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, 130041, Jilin, People's Republic of China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning, People's Republic of China.
J Exp Clin Cancer Res. 2019 Jan 8;38(1):7. doi: 10.1186/s13046-018-1020-z.
Increasing evidence supports the association of microRNA with tumor occurrence and development. However, the expression of miR-6875-3p and its role in cell proliferation, invasion and metastasis in hepatocellular carcinoma (HCC) remains elusive.
The expression of miR-6875-3p and BTG2 in HCC tissues and cell lines was detected by using in situ hybridization, immunohistochemistry and qRT-PCR, respectively. A western blot assay, qRT-PCR and Luciferase reporter assay were employed to study the interaction between miR-6875-3p and BTG2. Cell proliferation invasion and metastasis were measured by MTT, transwell and matrigel analyses in vitro. In vivo, tumorigenicity and metastasis assays were performed in nude mice.
We found that miR-6875-3p were elevated expressed in HCC tissues and cell lines, and negatively correlated with BTG2 expression, while positively correlated with tumor staging, size, degree of differentiation, and vascular invasion of HCC. Moreover, in vitro and in vivo assays showed that miR-6875-3p regulates EMT and improve the proliferation, metastasis and stem cell-like properties of HCC cells. BTG2 was identified as a direct and functional target of miR-6875-3p via the 3'-UTR of BTG2. We also confirmed that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway.
Our study provides evidence that high expression of miR-6875-3p can promote tumorigenesis of HCC in vitro and in vivo, so as to function as a novel oncogene in HCC. In mechanism, we found that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway.
越来越多的证据支持 microRNA 与肿瘤的发生和发展有关。然而，miR-6875-3p 的表达及其在肝细胞癌（HCC）中细胞增殖、侵袭和转移中的作用仍不清楚。
采用原位杂交、免疫组化和 qRT-PCR 分别检测 HCC 组织和细胞系中 miR-6875-3p 和 BTG2 的表达。采用 Western blot 检测、qRT-PCR 和荧光素酶报告基因检测研究 miR-6875-3p 与 BTG2 之间的相互作用。体外通过 MTT、Transwell 和 Matrigel 分析测定细胞增殖、侵袭和转移。体内，在裸鼠中进行肿瘤发生和转移测定。
我们发现 miR-6875-3p 在 HCC 组织和细胞系中高表达，与 BTG2 表达呈负相关，与 HCC 的肿瘤分期、大小、分化程度和血管浸润程度呈正相关。此外，体外和体内实验表明，miR-6875-3p 通过 EMT 调节，改善 HCC 细胞的增殖、转移和干细胞样特性。BTG2 是 miR-6875-3p 的直接和功能靶基因，通过 BTG2 的 3'-UTR。我们还证实 miR-6875-3p 通过 BTG2/FAK/Akt 通路发挥其生物学功能。
我们的研究提供了证据表明，miR-6875-3p 的高表达可以促进 HCC 在体外和体内的肿瘤发生，从而作为 HCC 的一种新的癌基因发挥作用。在机制上，我们发现 miR-6875-3p 通过 BTG2/FAK/Akt 通路发挥其生物学功能。
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