Li Hongle, Jia Jinlin, Yang Lijun, Chu Jie, Sheng Jinxiu, Wang Chang, Meng Weiwei, Jia Zimo, Yin Huiqing, Wan Junhu, He Fucheng
Department of Molecular Pathology, The Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China.
Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Onco Targets Ther. 2020 Dec 22;13:13097-13109. doi: 10.2147/OTT.S286627. eCollection 2020.
Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy, which has posed a great challenge to public health, especially in China. Dysregulation of long non-coding RNAs is involved in the occurrence, development, invasion, and metastasis of multiple cancers including ESCC. However, little is known about the function of MIR205HG in ESCC.
We used qRT-PCR to detect the expression level of MIR205HG, miR-214, and SOX4 in human ESCC tissues and cell lines. Loss-of-functional assays were performed to test the impact of MIR205HG on cell proliferation, metastasis, and apoptosis process via CCK-8, transwell, and flow cell cytometry assays. Additionally, the downstream molecular mechanism of MIR205HG in ESCC was explored.
Here, we found MIR205HG was substantially up-regulated in ESCC, and there was a positive correlation between MIR205HG expression and tumor size and lymphatic metastasis of ESCC patients. Inhibition of MIR205HG attenuated cell proliferation, migration, and invasion. Silencing MIR205HG increased G1 phase cell counts and decreased S phase cell counts, along with increased apoptotic cell populations. Notably, the rescue assays indicated that miR-214 could partly reverse the influence of MIR205HG on ESCC cell migration. We also found that SOX4 was a direct target mRNA of miR-214, and MIR205HG could act as a molecular sponge to regulate SOX4 expression in ESCC.
Taken together, our findings demonstrate that MIR205HG promotes ESCC progression by regulating the miR-214/SOX4 axis. MIR205HG may be a novel candidate target for ESCC diagnosis and therapy.
食管鳞状细胞癌(ESCC)是一种常见的致命恶性肿瘤,对公众健康构成了巨大挑战,尤其是在中国。长链非编码RNA的失调与包括ESCC在内的多种癌症的发生、发展、侵袭和转移有关。然而,关于MIR205HG在ESCC中的功能知之甚少。
我们使用qRT-PCR检测人ESCC组织和细胞系中MIR205HG、miR-214和SOX4的表达水平。通过CCK-8、transwell和流式细胞术检测进行功能丧失实验,以测试MIR205HG对细胞增殖、转移和凋亡过程的影响。此外,还探索了MIR205HG在ESCC中的下游分子机制。
在此,我们发现MIR205HG在ESCC中显著上调,并且MIR205HG表达与ESCC患者的肿瘤大小和淋巴转移之间存在正相关。抑制MIR205HG可减弱细胞增殖、迁移和侵袭。沉默MIR205HG增加了G1期细胞计数并减少了S期细胞计数,同时增加了凋亡细胞群体。值得注意的是,挽救实验表明miR-214可以部分逆转MIR205HG对ESCC细胞迁移的影响。我们还发现SOX4是miR-214的直接靶标mRNA,并且MIR205HG可以作为分子海绵来调节ESCC中SOX4的表达。
综上所述,我们的研究结果表明MIR205HG通过调节miR-214/SOX4轴促进ESCC进展。MIR205HG可能是ESCC诊断和治疗的新候选靶点。