Functional assessment of miR‑1291 in colon cancer cells

Wang,Jiaqi; Yokoyama,Yuhki; Hirose,Haruka; Shimomura,Yuki; Bonkobara,Saki; Itakura,Hiroaki; Kouda,Shihori; Morimoto,Yoshihiro; Minami,Kazumasa; Takahashi,Hidekazu; Shibata,Satoshi; Kobayashi,Shogo; Uemura,Mamoru; Tanaka,Susumu; Wu,Xin; Tanaka,Shinji; Mori,Masaki; Yamamoto,Hirofumi

doi:10.3892/ijo.2022.5303

Functional assessment of miR‑1291 in colon cancer cells

Authors:
- Jiaqi Wang
- Yuhki Yokoyama
- Haruka Hirose
- Yuki Shimomura
- Saki Bonkobara
- Hiroaki Itakura
- Shihori Kouda
- Yoshihiro Morimoto
- Kazumasa Minami
- Hidekazu Takahashi
- Satoshi Shibata
- Shogo Kobayashi
- Mamoru Uemura
- Susumu Tanaka
- Xin Wu
- Shinji Tanaka
- Masaki Mori
- Hirofumi Yamamoto
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Affiliations: Department of Molecular Pathology, Division of Health Sciences, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Surgery and Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Radiation Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Surgery and Gastroenterological Surgery, Graduate School of Medicine, Osaka University,Suita, Osaka 565‑0871, Japan, First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113‑8510, Japan, Tokai University, Graduate School of Medicine, Isehara, Kanagawa 259‑1193, Japan
Published online on: January 4, 2022 https://doi.org/10.3892/ijo.2022.5303
Article Number: 13
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

miR‑1291 exerts an anti‑tumor effect in a subset of human carcinomas, including pancreatic cancer. However, its role in colorectal cancer (CRC) is largely unknown. In the present study, the expression and effect of miR‑1291 in CRC cells was investigated. It was identified that miR‑1291 significantly suppressed the proliferation, invasion, cell mobility and colony formation of CRC cells. Additionally, miR‑1291 induced cell apoptosis. A luciferase reporter assay revealed that miR‑1291 directly bound the 3'‑untranslated region sequence of doublecortin‑like kinase 1 (DCLK1). miR‑1291 also suppressed DCLK1 mRNA and protein expression in HCT116 cells that expressed DCLK1. Furthermore, miR‑1291 suppressed cancer stem cell markers BMI1 and CD133, and inhibited sphere formation. The inhibitory effects on sphere formation, invasion and mobility in HCT116 cells were also explored and verified using DCLK1 siRNAs. Furthermore, miR‑1291 induced CDK inhibitors p21^WAF1/CIP1 and p27^KIP1 in three CRC cell lines, and the overexpression of DCLK1 in HCT116 cells led to a decrease of p21^WAF1/CIP1 and p27^KIP1. Intravenous administration of miR‑1291 loaded on the super carbonate apatite delivery system significantly inhibited tumor growth in the DLD‑1 xenograft mouse model. Additionally, the resultant tumors exhibited significant upregulation of the p21^WAF1/CIP1 and p27^KIP1 protein with treatment of miR‑1291. Taken together, the results indicated that miR‑1291 served an anti‑tumor effect by modulating multiple functions, including cancer stemness and cell cycle regulation. The current data suggested that miR‑1291 may be a promising nucleic acid medicine against CRC.

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