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Circ_0091581 Promotes the Progression of Hepatocellular Carcinoma Through Targeting miR-591/FOSL2 Axis

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Abstract

Background

Circular RNAs (circRNAs) have shown crucial regulatory roles in cancer biology. We aimed to uncover the role and underlying mechanism of circ_0091581 in hepatocellular carcinoma (HCC) progression.

Methods

The abundance of circ_0091581, microRNA-591 (miR-591) and FOS like 2, AP-1 transcription factor subunit (FOSL2) was measured by quantitative real-time polymerase chain reaction. Cell viability, colony formation ability, and invasion ability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and transwell invasion assay. The migration ability was analyzed by transwell migration assay and wound healing assay. Flow cytometry was used to evaluate the cell cycle and apoptosis of HCC cells. The interaction between miR-591 and circ_0091581 or FOSL2 was predicted by Circular RNA Interactome database or TargetScan database and confirmed by dual-luciferase reporter assay and RNA immune co-precipitation assay. FOSL2 protein expression was measured by Western blot assay. Xenograft tumor assay was conducted to analyze the role of circ_0091581 in HCC tumor growth in vivo.

Results

Circ_0091581 was highly expressed in HCC tissue samples and cell lines in contrast to that in adjacent normal tissue samples and THLE-2 cell line. Circ_0091581 accelerated the viability, colony formation, metastasis, and cell cycle, while it impeded the apoptosis of HCC cells. MiR-591 bound to circ_0091581, and circ_0091581 knockdown-mediated effects in HCC cells were largely overturned by miR-591 silencing. FOSL2 was a target of miR-591, and FOSL2 overexpression largely reversed miR-591 accumulation-induced influences in HCC cells. FOSL2 protein expression was down-regulated by circ_0091581 silencing, and the addition of miR-591 inhibitor partly recovered the expression of FOSL2 in HCC cells. Circ_0091581 interference notably suppressed HCC tumor growth in vivo.

Conclusion

Circ_0091581 acted as an oncogene to enhance the viability, colony formation, metastasis and cell cycle and inhibit the apoptosis of HCC cells through targeting miR-591/FOSL2 axis.

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Abbreviations

HCC:

Hepatocellular carcinoma

qRT-PCR:

Quantitative real-time polymerase chain reaction

RIP:

RNA immune co-precipitation

FITC:

Fluorescein isothiocyanate

WT:

Wild type

MUT:

Mutant type

HRP:

Horseradish peroxidase

PVDF:

Polyvinylidene fluoride

ECL:

Enhanced chemiluminescent visualization

SD:

Standard deviation

ANOVA:

Analysis of variance

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Acknowledgments

None.

Funding

This work was supported by the Social Science and Technology Development Foundation of Dongguan, China (No. 202050715025194).

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Author notes

  1. Chenggang Ji and Xiaocheng Hong have contributed equally to this paper.

Authors and Affiliations

  1. Department of General Surgery, Binhaiwan Central Hospital of Dongguan, (also called The Fifth People’s Hospital of Dongguan), The Dongguan Affiliated Hospital of Medical College of Jinan University, No.111 Humen Road, Humen Town, Dongguan City, 523905, Guangdong Province, China

    Chenggang Ji, Xiaocheng Hong, Yingxin He, Jiayang Chen, Xi Liu, Weijie Ye, Zhikang Mo, Zhanpeng She & Shuwen Lin

  2. Department of Anorectal Surgery, Binhaiwan Central Hospital of Dongguan, (also called The Fifth People’s Hospital of Dongguan), The Dongguan Affiliated Hospital of Medical College of Jinan University, Dongguan City, Guangdong Province, China

    Bo Lan

  3. Department of General Surgery, Guangdong Provincial People’s Hospital, Guangzhou City, Guangdong Province, China

    Ye Lin

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  1. Chenggang Ji
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Correspondence to Shuwen Lin.

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Written informed consent was obtained from patients with approval by the Institutional Review Board in Binhaiwan Central Hospital of Dongguan (also called The Fifth People’s Hospital of Dongguan), The Dongguan Affiliated Hospital of Medical College of Jinan University.

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Ji, C., Hong, X., Lan, B. et al. Circ_0091581 Promotes the Progression of Hepatocellular Carcinoma Through Targeting miR-591/FOSL2 Axis. Dig Dis Sci 66, 3074–3085 (2021). https://doi.org/10.1007/s10620-020-06641-4

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