Abstract
BackgroundRecently, 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.
Highlights
MiR-22 is identified as a tumor-suppressing microRNA in many human cancers
We identified CD147 as a target gene for miR-22 to regulate the invasion and metastasis of hepatocellular carcinoma (HCC) cells in vitro. miR-22 might act as a tumor suppressor and serve as a potential therapeutic target in HCC
The expression of miR‐22 is downexpressed in HCC tissues and cell lines To identify the expression of miR-22 in the HCC, thirtyfour paired of HCC and normal tissues were measured by real time reverse transcription polymerase chain reaction (RT-PCR)
Summary
MiR-22 is identified as a tumor-suppressing microRNA in many human cancers. The involvement of miR-22 in CD147 regulation and hepatocellular carcinoma (HCC) progression and metastasis has not been investigated. Hepatocellular carcinoma (HCC) has become one of the most frequently occurring cancers, and is considered to be highly lethal, accounting for approximately onethird of cancer-related deaths worldwide [1, 2]. Current studies have shown that microRNAs (miRNAs) can act as activators or inhibitors of tumor metastasis by targeting multiple signaling pathways involved in metastasis [4,5,6]. MiR-22 is a 22-nt non-coding RNA and originally identified in HeLa cells as a tumor-suppressing miRNA. Several targets of miR-22 were reported to mediate its tumorsuppressive effect, such as tumor-suppressive PTEN, Max genes, p21, Sp1, CD147 and oncogene c-myc expression, etc. Several targets of miR-22 were reported to mediate its tumorsuppressive effect, such as tumor-suppressive PTEN, Max genes, p21, Sp1, CD147 and oncogene c-myc expression, etc. [7,8,9,10,11].
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