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Circ_0061140 Contributes to Ovarian Cancer Progression by Targeting miR-761/LETM1 Signaling

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Abstract

Previous studies have suggested that circular RNAs (circRNAs) play important regulatory roles in cancer progression. Previous evidence exhibited the aberrant upregulation of circ_0061140 in ovarian cancer. However, the detailed role of circ_0061140 in ovarian cancer progression and its associated mechanism remain largely unknown and need further exploration. The expression of circ_0061140, microRNA-761 (miR-761) and leucine zipper and EF-hand containing transmembrane protein 1 (LETM1) was checked by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blot. Cell Counting Kit-8 (CCK8), colony formation, 5-Ethynyl-2’-deoxyuridine (EdU), flow cytometry, wound healing, transwell, and tube formation assays were conducted to assess cell functions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the interaction between miR-761 and circ_0061140 or LETM1. Xenograft tumor model was established to analyze the role of circ_0061140 in tumor growth in vivo. Circ_0061140 expression was notably up-regulated in ovarian cancer tissues and cell lines. Circ_0061140 knockdown suppressed the proliferation, migration, invasion, and angiogenesis and triggered the apoptosis of ovarian cancer cells. Circ_0061140 directly interacted with miR-761, and circ_0061140 silencing-mediated anti-tumor effects were partly abolished by miR-761 knockdown in ovarian cancer cells. LETM1 was a direct target of miR-761, and LETM1 overexpression partly counteracted miR-761-induced anti-tumor effects. Circ_0061140 could up-regulate LETM1 expression by sponging miR-761. Circ_0061140 knockdown significantly suppressed xenograft tumor growth in vivo. Circ_0061140 aggravated ovarian cancer progression through miR-761-dependent regulation of LETM1.

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Data Availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Laboratory Medicine, The First Affiliated Hospital of Xi’An Jiaotong University, Xi’an, 710061, Shaanxi, China

    Lieting Ma

  2. Department of Hemodialysis, The First Affiliated Hospital of Xi’An Jiaotong University, Xi’an, 710061, Shaanxi, China

    Wenyan Liu

  3. Department of Radiology, The First Affiliated Hospital of Xi’An Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061, Shaanxi, China

    Miaoling Li

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  1. Lieting Ma
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Correspondence to Miaoling Li.

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Ethical Approval

The clinical study was approved by the ethical review committee of The First affiliated Hospital of Xi’An Jiaotong University. All the participants had signed the written informed consent. The protocol in animal study was approved by the ethical review committee of The First affiliated Hospital of Xi’An Jiaotong University.

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10528_2022_10277_MOESM1_ESM.tif

Supplementary file1 Figure S1 Circ_0061140 overexpression enhanced ovarian cancer cell proliferation, migration, invasion and angiogenesis. (A-G) SKOV3 and A2780 cells overexpressing circ_0061140 were used in the following assays. (A and B) Cell proliferation was evaluated by CCK8 assay. (C and D) Cell proliferation was evaluated by colony formation assay and EdU assay. (E and F) Cell migration and invasion were evaluated by wound healing assay and transwell assay. (G) The ability of angiogenesis was assessed by tube formation assay. (H and I) The expressions of PCNA, Bax, and Bcl-2 proteins were assessed by western blot. **p<0.01, ***p<0.001, ****p<0.0001 (TIF 4755 kb)

10528_2022_10277_MOESM2_ESM.tif

Supplementary file2 Figure S2. MiR-761 expression increased most in ovarian cancer cells after circ_0061140 knockdown. (A and B) The expression of predicted miRNAs in SKOV3 and A2780 cells transfected with si-circ_0061140 or si-NC was examined using RT-qPCR. **p<0.01, ***p<0.001, ****p<0.0001 (TIF 336 kb)

10528_2022_10277_MOESM3_ESM.tif

Supplementary file3 Figure S3. LETM1 expression decreased most in ovarian cancer cells after miR-761 enrichment. (A and B) The expression of predicted mRNAs in SKOV3 and A2780 cells transfected with miR-761 mimic or miR-NC was examined using RT-qPCR. **p<0.01, ***p<0.001, ****p<0.0001 (TIF 301 kb)

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Ma, L., Liu, W. & Li, M. Circ_0061140 Contributes to Ovarian Cancer Progression by Targeting miR-761/LETM1 Signaling. Biochem Genet 61, 628–650 (2023). https://doi.org/10.1007/s10528-022-10277-6

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