J Cancer 2021; 12(20):6155-6164. doi:10.7150/jca.61967 This issue

Research Paper

Inhibition of the cell migration, invasion and chemoresistance of colorectal cancer cells through targeting KLF3 by miR-365a-3p

Jing Li, MD1#, Rubing Mo, MD2#, Linmei Zheng, MD3✉

1. Department of Emergency Surgery, Hainan General Hospital, Hainan Affiliated hospital of Hainan medical university, Haikou, Hainan Province, 570311, China.
2. Department of Pneumology, Hainan General Hospital, Hainan Affiliated hospital of Hainan medical university, Haikou, Hainan Province, 570311, China.
3. Department of Obstetrics, Hainan General Hospital, Hainan Affiliated hospital of Hainan medical university, Haikou, Hainan Province, 570311, China.
#Co-first authors.

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Citation:
Li J, Mo R, Zheng L. Inhibition of the cell migration, invasion and chemoresistance of colorectal cancer cells through targeting KLF3 by miR-365a-3p. J Cancer 2021; 12(20):6155-6164. doi:10.7150/jca.61967. Available from https://www.jcancer.org/v12p6155.htm

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Abstract

Graphic abstract

Background: Metastasis and chemoresistance limit treatment efficacy of colorectal cancer (CRC) patients. MicroRNAs (miRNAs) have been believed to be candidate biomarkers for tumor cell proliferation, metastasis and chemoresistance, but the related molecular mechanisms are not clear for prognosis prediction.

Aims: We aimed to investigate the role of miR-365a-3p in metastasis and chemoresistance of CRC.

Methods: The expression levels of miR-365a-3p in clinical CRC tissues were analyzed. The effects of miR-365a-3p expression levels on tumor chemoresistance, invasion and migration were also determined. A dual luciferase reporter gene assay was used to determine the effect of miR-365a-3p on its target gene, Kruppel-like factor 3 (KLF3), and the effect of the miR-365a-3p/KLF3 axis on CRC cell chemoresistance, migration and invasion was further investigated.

Results: In patients with CRC with lymph node or distant organ metastasis or in CRC cell lines, the expression levels of miR-365a-3p were significantly downregulated. In addition, the findings of Transwell assays demonstrated that miR-365a-3p significantly suppressed CRC cell migration and invasion. The dual luciferase reporter gene assay results suggested that miR-365a-3p may play an important role in the regulation of migration, invasion and chemoresistance in CRC cells.

Conclusions: The findings of present study provided evidence to suggest that miR-365a-3p may be a potential tumor suppressor gene in CRC and may inhibit the migration, invasion and chemoresistance of CRC cells. These results suggested that targeting miR-365a-3p/KLF3 axis may represent a potential therapeutic intervention for metastatic disease in patients with CRC.

Keywords: Colorectal cancer, Chemo-resistance, MicroRNAs, KLF3, Migration, Invasion