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Circ_0006948 Contributes to Cell Growth, Migration, Invasion and Epithelial–Mesenchymal Transition in Esophageal Carcinoma

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Abstract

Background

Circular RNAs (circRNAs) can act as promoters or inhibitors in cancer progression. Has_circ_0006948 (circ_0006948) was reported to aggravate the malignant behaviors of esophageal carcinoma (EC).

Aims

This study focused on investigating the molecular mechanism of circ_0006948 in EC progression.

Methods

The quantitative real-time polymerase chain reaction was performed to detect the expression of circ_0006948, microRNA-4262 (miR-4262) and fibronectin type III domain containing 3B (FNDC3B). Cell growth analysis was conducted by Cell Counting Kit-8 and colony formation assays. Cell migration and invasion were assessed by transwell assay. Epithelial–mesenchymal transition (EMT)-associated proteins and FNDC3B protein expression were assayed using western blot. Dual-luciferase reporter and RNA pull-down assays were performed to validate the target combination. Xenograft tumor assay was used for investigating the role of circ_0006948 in vivo.

Results

Circ_0006948 was upregulated in EC tissues and cells. Downregulating the expression of circ_0006948 or FNDC3B repressed cell growth, migration, invasion and EMT in EC cells. Target analysis indicated that miR-4262 was a target for circ_0006948 and FNDC3B was a downstream gene for miR-4262. Moreover, circ_0006948 could affect the expression of FNDC3B via sponging miR-4262. The effects of si-circ_0006948#1 on EC cells were partly restored by miR-4262 inhibition or FNDC3B overexpression. In addition, circ_0006948 also facilitated EC tumorigenesis in vivo by targeting the miR-4262/FNDC3B axis.

Conclusion

Taken together, circ_0006948 functioned as an oncogenic factor in EC by the miR-4262-mediated FNDC3B expression regulation.

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Authors and Affiliations

  1. Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China

    Meng Yue, Yakun Jiang, Jianmei Pan, Shuhong Zhang & Xingjie Shen

  2. Department of Oncology, Shengli Oil Central Hospital, Dongying City, Shandong Province, China

    Yanxia Liu

  3. Department of Oncology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province, China

    Taiyang Zuo

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  1. Meng Yue
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Correspondence to Meng Yue.

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Supplementary Fig. 1

The anti-tumor regulation of si-circ_0006948#1 was reversed by miR-4262 inhibitor. (A–K) Cellular assays were performed by CCK-8 (A–B) and colony formation assay (C–D) for cell growth, transwell assay for cell migration (F–G) and invasion (H–I), and western blot for EMT-related protein detection after transfection of si-NC, si-circ_0006948#1, si-circ_0006948#1+anti-NC or si-circ_0006948#1+anti-miR-4262. **P < 0.01, ***P < 0.001.

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Yue, M., Liu, Y., Zuo, T. et al. Circ_0006948 Contributes to Cell Growth, Migration, Invasion and Epithelial–Mesenchymal Transition in Esophageal Carcinoma. Dig Dis Sci 67, 492–503 (2022). https://doi.org/10.1007/s10620-021-06894-7

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  • DOI: https://doi.org/10.1007/s10620-021-06894-7

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