Wu Ju, Huang Jiaobao, Wang Wei, Xu Jian, Yin Min, Cheng Nan, Yin Jiajun
Cancer Biomark. 2017 Jul 19;20(1):55-65. doi: 10.3233/CBM-170090.
Long non-coding RNAs (lncRNAs) are aberrantly expressed in various cancers. Fer-1-like protein 4 (FER1L4), one of lncRNAs, plays a role as tumor suppressor in various human cancers and can be regulated by microRNA. However, the role and function of FER1L4 in human hepatocellular carcinoma (HCC) remains unknown. The aim of the present study was to annotate the role of FER1L4 and its clinical value in HCC. In the present study, we found that FER1L4 was lowly expressed in HCC tissue specimens as well as in malignant HCC cell lines, while the situation is opposite in miR-106a-5p. We found that down-regulated FER1L4 increased the expression of miR-106a-5p significantly and there was a reciprocal repression between FER1L4 and miR-106a-5p. Moreover, we identified FER1L4 as a target of miR-106a-5p by using dual-luciferase reporter assay. Knockdown of FER1L4 promoted the malignancy of HCC cells, including proliferation, migration, and invasion, and inhibited cell apoptosis. We also found that FER1L4 functions as a tumor suppressor in vivo. Together, these results suggest that FER1L4 could exert a tumor suppressive impact on HCC, which at least, in part, through suppressing miR-106a-5p expression. FER1L4, as well as miR-106a-5p, can predict the clinical prognosis of HCC alone or combined, which may be a novel therapeutic target for treating HCC.
长链非编码RNA(lncRNAs)在多种癌症中异常表达。Fer-1样蛋白4(FER1L4)作为lncRNAs之一,在多种人类癌症中发挥肿瘤抑制作用,且可受微小RNA调控。然而,FER1L4在人类肝细胞癌(HCC)中的作用和功能仍不清楚。本研究的目的是阐明FER1L4在HCC中的作用及其临床价值。在本研究中,我们发现FER1L4在HCC组织标本以及恶性HCC细胞系中低表达,而miR-106a-5p的情况则相反。我们发现下调的FER1L4显著增加了miR-106a-5p的表达,并且FER1L4与miR-106a-5p之间存在相互抑制作用。此外,我们通过双荧光素酶报告基因检测确定FER1L4是miR-106a-5p的靶标。敲低FER1L4促进了HCC细胞的恶性程度,包括增殖、迁移和侵袭,并抑制细胞凋亡。我们还发现FER1L4在体内发挥肿瘤抑制作用。总之,这些结果表明FER1L4可能对HCC发挥肿瘤抑制作用,这至少部分是通过抑制miR-106a-5p的表达来实现的。FER1L4以及miR-106a-5p单独或联合使用均可预测HCC的临床预后,这可能是治疗HCC的一个新的治疗靶点。