Abstract
Hepatocellular carcinoma (HCC) predominantly occurs in patients with chronic liver disease, accounting for 70–90% of all liver cancer cases. The role of circFOXM1/miR-1179/SPAG5 axis in HCC has not been reported. This study aimed to explore the regulatory mechanism of circFOXM1 in HCC proliferation and metastasis. RNA polymerase inhibitor actinomycin D and RNase R exonuclease were used to identify circFOXM1 in HCC cells. The qRT-PCR was used to detect circFOXM1 expression. Specific siRNA for circFOXM1 was designed, and the sequence of circFOXM1 was inserted in pLCDH-ciR to overexpress circFOXM. Cell proliferation was detected by CCK8 in vitro, by tumor volume and tumor weight of HCC xenograft in vivo. Cell migration was detected by transwell test. Binding status of circFOXM1 with miR-1179 was detected by luciferase reporter gene assay. Rescue experiments were applied to identify the oncogenic mechanism of circFOXM1 in HCC cells. Actinomycin D assay confirmed the cyclization of circFOXM1. RNase R treatment showed that circFOXM1 was not affected by RNase R exonuclease. CCK8 assay, tumor volume and tumor weight showed that circFOXM1 effectively promoted HCC cell proliferation. Transwell assay showed that circFOXM effectively promoted migration and invasion abilities of HCC cells. Luciferase reporter gene activity assay showed that miR-1179 had complementary binding sites with circFOXM1 and SPAG5. CircFOXM1 silencing inhibited malignant phenotypes in HCC cells were partly rescued by either miR-1179 silencing or SPAG5 overexpression. CircFOXM1 promoted HCC cell proliferation and metastasis by regulating miR-1179/SPAG5 axis.
Highlights
Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for about 70–90%
We revealed that circFOXM1 expression was significantly upregulated in HCC cells and tissues; the circFOXM1/miR-1179/sperm-associated antigen 5 (SPAG5) axis played an important regulatory role in the biological process of HCC, which provided a theoretical basis for the diagnosis and treatment of HCC
The stability of circFOXM1 in HCC cells was further investigated using Huh[7] cells. After both the circFOXM1 and FOXM1 in Huh[7] cells were exposed to Actinomycin D (Fig. 1B) or Ribonuclease R (RNase R, Fig. 1C), the expressions of circFOXM1 and FOXM1 were detected by qRT-PCR respectively, which revealed that circFOXM1 was more stable and more resistant to RNase R digestion than FOXM1
Summary
Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for about 70–90%. CircCCDC9 regulates CAV1 expression by directly targeting miR-6792-3p cavernous body, thereby inhibiting the development of gastric c ancer[8]; circTADA2A plays a role in the biological progress of osteosarcoma through the miR-203a-3p/CREB3 axis[9]; circRNA FOXM1 has been reported to sponge miR-1179, thereby accelerating the progression of papillary thyroid c arcinoma[10]. CircRNA_100290 sponging miR-29 plays an important role in the biological progression of oral squamous cell c arcinoma[15]. We revealed that circFOXM1 expression was significantly upregulated in HCC cells and tissues; the circFOXM1/miR-1179/SPAG5 axis played an important regulatory role in the biological process of HCC, which provided a theoretical basis for the diagnosis and treatment of HCC
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