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Has_circ_ASH1L acts as a sponge for miR-1254 to promote the malignant progression of cervical cancer by targeting CD36

Cancer Gene Therapy volume 32, pages 214–226 (2025)Cite this article

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Abstract

Cervical cancer (CC) is a prevalent gynecological malignancy. Increasing evidence suggests that circular RNAs (circRNAs) play a pivotal role in the pathogenesis of CC. However, the regulatory function of circ_ASH1L in CC remains elusive. In this study, we aim to elucidate the precise role and underlying mechanism of circ_ASH1L in the malignant progression of CC. The human CC dataset GSE102686 was extracted from the Gene Expression Omnibus (GEO) database for the analysis of differentially expressed circRNAs. Target gene prediction softwares were utilized to predict the binding of miRNAs to circ_ASH1L sponge. The expression level of circ_ASH1L in CC tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The characteristics of circ_ASH1L were determined by RNase R digestion, actinomycin D, and nucleo-plasmic separation assays. The effects of circ_ASH1L, miR-1254, and CD36 gain-and-loss on the malignant progression of CC were investigated using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound scratch, transwell, and Western blot assay. The effect of circ_ASH1L on tumorigenicity of CC cells in vivo was evaluated in nude mice through tumor xenograft assay. The targeted regulatory relationship between circ_ASH1L/miR-1254 as well as miR-1254/CD36 was validated by dual-luciferase reporter assay. We screened the differentially expressed circ_ASH1L from the GEO dataset GSE102686 and confirmed its circular structure. Furthermore, we observed a significant upregulation of circ_ASH1L in both CC tissues and cells. Overexpression of circ_ASH1L promotes proliferation, invasion, and migration of CC cells while inhibiting cell apoptosis. However, silencing circ_ASH1L showed opposite results and inhibited tumorigenicity of CC cells in nude mice. Furthermore, we have identified circ_ASH1L as a miR-1254 sponge in CC cells. Notably, our in vitro experiments demonstrated that exogenously modulating the expression of miR-1254 effectively counteracted the impact of circ_ASH1L on the malignant phenotypic characteristics of CC cells. Similarly, modulation of CD36 expression efficiently counteracted the effect of miR-1254 on the malignant biological behavior of CC cells. In conclusion, circ_ASH1L promoted the malignant progression of CC via upregulating CD36 expression through sponging miR-1254.

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Fig. 1: Circ_ASH1L was highly expressed in CC tissues and cell lines.
Fig. 2: Impacts of circ_ASH1L on the proliferation, apoptosis, migration, invasion, and tumorigenesis of CC cells.
Fig. 3: Circ_ASH1L modulated the expression of miR-1254 through sponge adsorption in CC cells.
Fig. 4: Circ_ASH1L exerted its role in CC cells via sponging miR-1254.
Fig. 5: CD36 was a downstream target of miR-1254 in CC cells.
Fig. 6: miR-1254 regulated the biological processes of CC cells via targeting CD36.
Fig. 7

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (grant nos. 81771618 and 81971356).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China

    Jun Zhang, Yan Zhang, Xing Li & Yindi Bao

  2. Reproductive Medical Center/Hubei Medical Clinical Research Center for Assisted Reproductive Technology and Embryonic Development, Renmin Hospital of Wuhan University, Wuhan, China

    Jing Yang

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Contributions

JZ contributed to the most experimental studies, and drafted the manuscript; YZ and XL analyzed data and revised the paper; YDB and JY contributed to the study design and concepts, literature research, statistical analysis, manuscript review. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yindi Bao or Jing Yang.

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Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

The study was granted approval by the Ethics Review Committee of Renmin Hospital of Wuhan University (approval number: WDRY2022-K277), conducted in accordance with the Helsinki Declaration. Written informed consent was obtained from all enrolled patients. The procedures for care and use of animals were approved by the Ethics Committee of Besser Model Biology Center (approval number: BSMS No. 2023-04-24 A), which adhered to the Guidelines for the Ethical Welfare Review of Laboratory Animals issued by the Ministry of Science and Technology of China (GB/T 35892-2018).

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Zhang, J., Zhang, Y., Li, X. et al. Has_circ_ASH1L acts as a sponge for miR-1254 to promote the malignant progression of cervical cancer by targeting CD36. Cancer Gene Ther 32, 214–226 (2025). https://doi.org/10.1038/s41417-024-00866-5

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