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Circ_0000467 Exerts an Oncogenic Role in Colorectal Cancer via miR-330-5p-Dependent Regulation of TYRO3

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Abstract

Colorectal cancer (CRC) remains one of the most frequent neoplasms of digestive tract worldwide. Circular RNAs (circRNAs) have been identified to serve crucial regulatory roles in the pathogenesis of human cancers. However, the role and regulatory mechanism of circ_0000467 in the progression of CRC are still unclear. The expression levels of circ_0000467, microRNA-330-5p (miR-330-5p), and tyrosine receptor kinase 3 (TYRO3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-330-5p and circ_0000467 or TYRO3 was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft tumor assay and Immunohistochemistry (IHC) assay were implemented to analyze CRC tumor growth in vivo. Circ_0000467 was a stable circRNA and was highly expressed in CRC tumor tissues and cells. Silencing of circ_0000467 could inhibit the proliferation, migration, invasion, and glycolysis and accelerated the apoptosis of CRC cells in vitro and hindered tumor growth in vivo. Mechanistically, circ_0000467 directly interacted with miR-330-5p and circ_0000467 depletion inhibited CRC cell malignant progression by regulating miR-330-5p. Furthermore, TYRO3 was a target of miR-330-5p and circ_0000467 upregulated TYRO3 expression by sponging miR-330-5p. Moreover, TYRO3 overexpression counteracted the inhibitory effect of miR-330-5p overexpression or circ_0000467 knockdown on CRC cell progression. Altogether, circ_0000467 knockdown suppressed CRC cell malignant development through modulating the miR-330-5p/TYRO3 network, providing a novel molecular target of CRC therapy.

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Authors and Affiliations

  1. Department of Anorectal Surgery, Huizhou Municipal Central Hospital, No. 12, Eling North Road, Huicheng District, Huizhou City, 516001, Guangdong Province, China

    Yubao Huang, Zhiyu Chen, Xiong Zhou & Hai Huang

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  1. Yubao Huang
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  2. Zhiyu Chen
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  3. Xiong Zhou
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  4. Hai Huang
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Contributions

HH designed and performed the research; ZC and XZ analyzed the data; YH wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yubao Huang.

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Written informed consents were obtained from all participants and this study was permitted by the Ethics Committee of Huizhou Municipal Central Hospital.

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Supplementary Information

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10528_2021_10171_MOESM1_ESM.tif

Supplementary file1 (TIF 5992 KB) The effects of miR-382-5p and miR-330-5p on the malignant behaviors of CRC cells. HCT116 and LoVo cells transfected with anti-miR-NC, anti-miR-330-5p, anti-miR-382-5p, and anti-miR-330-5p + anti-miR-382-5p. (A and B) CCK8 assay was used to evaluate the proliferation of transfected cells. (C) Cell migration ability was detected by transwell assay. *P < 0.05

10528_2021_10171_MOESM2_ESM.tif

Supplementary file2 (TIF 450 KB) The protein levels of miR-330-5p-targeted genes in CRC cells with miR-330-5p transfection. (A and B) The protein levels of ERBB4, FZD5, TYRO3, PAK2, and XIAP in HCT116 and LoVo cells transfected with miR-NC or miR-330-5p were detected by western blot assay. *P < 0.05, **P < 0.01, ***P < 0.001

10528_2021_10171_MOESM3_ESM.tif

Supplementary file3 (TIF 7681 KB) Circ_0000467 regulated the progression of CRC by regulating TYRO3 expression. HCT116 and LoVo cells were transfected with si-NC, si-circ_0000467#2, si-circ_0000467#2 + pcDNA, or si-circ_0000467#2 + TYRO3, respectively. (A and B) The proliferation of transfected cells was detected by CCK8 assay. (C–E) Flow cytometry assay was employed to detect the apoptosis and cell cycle distribution of transfected cells. (F and G) The migration and invasion abilities of transfected cells were detected by transwell assay. (H and I) The protein levels of E-cadherin, N-cadherin, and Vimentin were analyzed by western blot assay. (J–L) The levels of glucose uptake, lactate production, and ATP production were evaluated by corresponding kits. *P < 0.05

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Huang, Y., Chen, Z., Zhou, X. et al. Circ_0000467 Exerts an Oncogenic Role in Colorectal Cancer via miR-330-5p-Dependent Regulation of TYRO3. Biochem Genet 60, 1488–1510 (2022). https://doi.org/10.1007/s10528-021-10171-7

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