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Knockdown of circRAD23B Exerts Antitumor Response in Colorectal Cancer via the Regulation of miR-1205/TRIM44 axis

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Abstract

Background

Colorectal cancer (CRC) is a common cancer with high metastatic property. Circular RNAs (circRNAs) have important involvement in cancer processes. This study focused on the regulation of circRNA RAD23 homologue B (circRAD23B) in CRC.

Methods

The levels of circRAD23B, microRNA-1205 (miR-1205), and tripartite motif-44 (TRIM44) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Functional analyses were performed by Cell Counting Kit-8 (CCK-8) for cell proliferation, flow cytometry for cell cycle or cell apoptosis, and transwell assay for cell migration and invasion. Western blot was administrated for protein detection. The interaction of targets was analyzed by dual-luciferase reporter and RNA pull-down assays. The in vivo experiment was conducted via xenograft tumor in mice.

Results

We identified that circRAD23B was overexpressed in CRC tissues and cells. CRC cell proliferation, cell cycle progression, and cell metastasis were inhibited, while apoptosis was promoted by downregulating circRAD23B. Target analysis indicated that circRAD23B-targeted miR-1205 and TRIM44 were downstream genes of miR-1205. Moreover, the antitumor response of circRAD23B downregulation and miR-1205 overexpression was, respectively, achieved by increasing miR-1205 and decreasing TRIM44. CircRAD23B could regulate TRIM44 level by sponging miR-1205. In vivo, circRAD23B knockdown also reduced CRC tumorigenesis via the miR-1205/TRIM44 axis.

Conclusion

These results suggested that the inhibition of circRAD23B retarded the progression of CRC via acting on the miR-1205/TRIM44 axis. CircRAD23B might be a novel target in CRC treatment.

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Funding

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Authors and Affiliations

  1. Department of Gastroenterology, Weifang No.2 People’s Hospital, Weifang, Shandong, China

    Bingbing Han

  2. Department of Health, Weifang No.2 People’s Hospital, Weifang, Shandong, China

    Xiaohong Wang

  3. Department of Neurology, Weifang No.2 People’s Hospital, No.7 Yuanxiao Street, Kuiwen District 261042, Weifang, Shandong, China

    Xia Yin

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  1. Bingbing Han
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  3. Xia Yin
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Correspondence to Xia Yin.

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Supplementary Information

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10620_2021_6859_MOESM1_ESM.tif

Supplementary Fig.1. MiR-1205 was used as the target research for circRAD23B. (A) Venn diagram was performed to seek the potential targets for circRAD23B from the predicted miRNAs by circinteractome and circBank. (B) The expression levels of miR-1205, miR-1253, miR-892b and miR-935 were detected in SW480 cells transfected with si-NC or si-RAD23B#2. All experiments were performed three times (N=3). *P < 0.05. (TIF 365 kb)

10620_2021_6859_MOESM2_ESM.tif

Supplementary Fig.2. TRIM44 upregulation in colon adenocarcinoma. The dataset analysis of TRIM44 expression in 471 cancer and 41 normal samples. (TIF 367 kb)

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Han, B., Wang, X. & Yin, X. Knockdown of circRAD23B Exerts Antitumor Response in Colorectal Cancer via the Regulation of miR-1205/TRIM44 axis. Dig Dis Sci 67, 504–515 (2022). https://doi.org/10.1007/s10620-021-06859-w

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  • DOI: https://doi.org/10.1007/s10620-021-06859-w

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