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LncRNA BBOX1-AS1 Contributes to the Progression of Esophageal Carcinoma by Targeting the miR-361-3p/COL5A1 Axis

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Abstract

Long noncoding RNAs (lncRNAs) are known to participate in the progression of several cancers, including esophageal carcinoma (EC), a common malignancy of the digestive system. Although the role of the lncRNA-miRNA-mRNA regulatory network is crucial for the growth and progression of EC, the regulation of lncRNA BBOX1-AS1 (BBOX1 antisense RNA1) remains unclear. We performed reverse transcription-quantitative PCR (RT-qPCR) and western blotting to evaluate miR-361-3p, collagen type V alpha 1 chain (COL5A1), and BBOX1-AS1 expression levels in EC cells and tissues. The colony formation assay (CFA) and Cell Counting Kit-8 (CCK-8) were employed to identify EC cell proliferation, while western blotting was used to examine EC cell apoptosis and Bax and Bcl-2 expression levels. The effect of BBOX1-AS1 on EC proliferation was determined using an in vivo carcinogenesis assay. Correlation between COL5A1, BBOX1-AS1, and miR-361-3p was examined using the luciferase reporter system and RNA immunoprecipitation assay (RIP). Herein, we observed that BBOX1-AS1 expression levels were upregulated in EC cells and tissues. BBOX1-AS1 knockdown inhibited EC cell proliferation and conferred a pro-apoptotic effect. These results indicated a positive interaction between BBOX1-AS1 and miR-361-3p in EC and a negative association with miR-361-3p. COL5A1 was recognized as a downstream miR-361-3p target and was inversely related to miR-361-3p in EC. Therefore, BBOX1-AS1 expression suppressed cell apoptosis and promoted cell proliferation via the downregulation of miR-361-3p and upregulation of COL5A1 expression. Overall, BBOX1-AS1 facilitates EC progression via the miR-361-3p or COL5A1 axis, indicating that BBOX1-AS1 might be a potential therapeutic target for EC therapy.

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Data Availability

The datasets used and/or analyzed throughout this present investigation are available from the relevant author upon proper request.

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  1. Yu-Hai Lu and Dong-Sheng He have contributed equally to this work.

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  1. Department of Cardiothoracic Surgery, First Affiliated Hospital of Chengdu Medical College, No. 278, Middle Section of Baoguang Avenue, Xindu District, Chengdu, 610500, Sichuan, China

    Yu-Hai Lu, Dong-Sheng He, Ying Li, Hong Wang & Rui-Dong Ma

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Contributions

YHL conducted the experiments and data analysis. DSH conceived and designed this study. RDM formed the methodology. YL did investigation. HW authored the paper. This manuscript was reviewed and revised by YHL and DSH. This work has been reviewed and approved by all authors.

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Correspondence to Hong Wang or Rui-Dong Ma.

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The First Affiliated Hospital of Chengdu Medical College’s Ethics Committee approved this study (Chengdu, China). The World Medical Association’s Helsinki Declaration was followed in the conduct of this study. Informed consent papers were signed by each patient. The ethical committee of First Affiliated Hospital of Chengdu Medical College gave its approval to this study. The ARRIVE standards have been strictly followed in all of the animal investigations.

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Lu, YH., He, DS., Li, Y. et al. LncRNA BBOX1-AS1 Contributes to the Progression of Esophageal Carcinoma by Targeting the miR-361-3p/COL5A1 Axis. Biochem Genet 61, 1351–1368 (2023). https://doi.org/10.1007/s10528-022-10307-3

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