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Combinatorial Chemistry & High Throughput Screening

Author(s): Lizhong Peng*, Pan Li and Zexu Peng

DOI: 10.2174/1386207326666230504144758

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miR-141-3p Enhanced Radiosensitivity of CRC Cells

Page: [118 - 126] Pages: 9

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Abstract

Background: Colorectal cancer (CRC) is recognized as one of the frequently diagnosed malignancies, and numerous microRNAs (miRs) are identified to be active in CRC.

Objective: This work aimed to clarify the effect of miR-141-3p on the radiosensitivity of CRC cells.

Methods: Firstly, CRC cell lines were cultured and applied to construct radiation-resistant CRC cells via X-ray treatment. The expression levels of miR-141-3p and long non-coding RNA DLX6 antisense RNA 1 (lncRNA DLX6-AS1) in CRC cells were measured using real-time quantitative polymerase chain reaction. After transfection with miR-141-3p mimics and 24 h treatment with 6- MV X-ray (0, 2, 4, 6 Gy), the survival fraction (SF) and the colony formation ability of CRC cells were determined using the cell counting kit-8 and colony formation methods. The interactions between miR-141-3p and DLX6-AS1 were analyzed using the dual-luciferase assay. The impact of miR-141-3p on DLX6-AS1 stability was detected after adding actinomycin-D. The role of DLX6- AS1 in the radiosensitivity of CRC cells was explored by transfecting oe-DLX6-AS1 into radiation- resistant CRC cells overexpressing miR-141-3p.

Results: The relative expression levels of miR-141-3p were downregulated in CRC cells and further declined in radiation-resistant cells. Upregulation of miR-141-3p relative expression reduced SF and the colony formation ability while amplifying the radiosensitivity of radiation-resistant CRC cells. miR-141-3p directly bound to DLX6-AS1 to reduce DLX6-AS1 stability, and therefore downregulated DLX6-AS1 expression. DLX6-AS1 overexpression counteracted the role of miR- 141-3p overexpression in amplifying the radiosensitivity of radiation-resistant CRC cells.

Conclusion: miR-141-3p binding to DLX6-AS1 significantly decreased DLX6-AS1 stability and expression, promoting the radiosensitivity of CRC cells.

Keywords: Colorectal cancer, miR-141-3p, lncRNA DLX6-AS1, radiotherapy, radiosensitivity, RNA stability, colon cancer, rectal cancer.

Graphical Abstract

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