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The inhibition role of miR-22 in hepatocellular carcinoma cell migration and invasion via targeting CD147

机译:miR-22通过靶向CD147抑制肝癌细胞迁移和侵袭的作用

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Background Recently, miR-22 is identified as a tumor-suppressing microRNA in many human cancers. CD147 is a novel cancer-associated biomarker that plays an important role in the invasion and metastasis of malignant tumor. However, the involvement of miR-22 in CD147 regulation and hepatocellular carcinoma (HCC) progression and metastasis has not been investigated. Methods We measured miR-22 expression level in 34 paired of HCC and matched normal tissues, HCC cell lines by real-time quantitative RT-PCR. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of HCC cell after overexpression of miR-22. The effect of miR-22 on HCC in vivo was validated by murine xenograft model. The relationship of miR-22 and its target gene CD147 was also investigated. Results We found that the expression of miR-22 in HCC tissues and cell lines were much lower than that in normal control, respectively. The expression of miR-22 was inversely correlated with HCC metastatic ability. Moreover, overexpression of miR-22 could significantly inhibit the HCC cell proliferation, migration and invasion in vitro and decrease HCC tumor growth in vivo. Finally, we found that miR-22 interacted with CD147 and decreased its expression, via a specific target site within the CD147 3′UTR by luciferase reporter assay. The expression of CD147 was inversely correlated with miR-22 expression in HCC tissues. Conclusion Our results suggested that miR-22 was downexpressed in HCC and inhibited HCC cell proliferation, migration and invasion through downregulating cancer-associated gene CD147 which may provide a new bio-target for HCC therapy.
机译:背景技术最近,在许多人类癌症中,miR-22被鉴定为一种抑制肿瘤的microRNA。 CD147是一种新型的癌症相关生物标志物,在恶性肿瘤的侵袭和转移中起着重要的作用。但是,尚未研究miR-22参与CD147调节和肝细胞癌(HCC)的进展和转移。方法我们通过实时定量RT-PCR检测34对配对的HCC和正常组织,HCC细胞株中miR-22的表达水平。在miR-22过表达后,进行侵袭测定,MTT增殖测定和伤口愈合测定以测试HCC细胞的侵袭和增殖。通过鼠异种移植模型证实了miR-22对体内HCC的作用。还研究了miR-22及其靶基因CD147的关系。结果我们发现miR-22在肝癌组织和细胞系中的表达分别比正常对照组低得多。 miR-22的表达与肝癌转移能力呈负相关。此外,miR-22的过表达可在体外显着抑制HCC细胞的增殖,迁移和侵袭,并在体内降低HCC肿瘤的生长。最后,我们通过荧光素酶报告基因检测发现,miR-22通过CD147 3'UTR中的特定靶位点与CD147相互作用并降低其表达。在肝癌组织中,CD147的表达与miR-22的表达呈负相关。结论我们的结果表明miR-22在HCC中表达降低,并通过下调癌症相关基因CD147抑制HCC细胞增殖,迁移和侵袭,这可能为HCC治疗提供新的生物学靶标。

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