Abstract
MicroRNAs (miRNAs/miRs) are a class of small non-coding RNAs that play pivotal roles in cancer physiology as important epigenetic regulators of gene expression. Several miRNAs have been previously discovered that regulate the proliferation of the colorectal cancer (CRC) cell line HCT116. In the present study, one of these miRNAs, miR-5191, was characterized as a tumor suppressor in CRC cells. Transfection with miR-5191 led to a significant decrease in cell proliferation, invasiveness, tumor sphere-forming ability and tumor organoid growth, as determined via trypan blue, Transwell, sphere culture and organoid culture assays, respectively. Flow cytometric analyses revealed that miR-5191 induced the cell cycle arrest and apoptosis of CRC cells. Additionally, the expression of miR-5191 was downregulated in CRC tumor tissues compared with in normal tissues, as measured by reverse transcription-quantitative PCR analysis. Ribosomal protein S6 kinase β1 (RPS6KB1) was identified as a direct target of miR-5191. Ectopic expression of RPS6KB1 suppressed the function of miR-5191. Intratumoral injection of miR-5191 mimic suppressed tumor growth in HCT116 xenografts. These findings suggested a novel tumor-suppressive function for miR-5191 in CRC, and its potential applicability for the development of anticancer miRNA therapeutics.
Original language | English |
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Pages (from-to) | 960-972 |
Number of pages | 13 |
Journal | International journal of oncology |
Volume | 55 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2019 |
Bibliographical note
Funding Information:This work was supported by a grant of the Korea Institute of Radiological and Medical Sciences, funded by the Ministry of Science and ICT, Republic of Korea (grant no. 50531-2019) and in part by a grant from the National Research Foundation of Korea (grant no. NRF-2017R1A2B2004055 to YHH).
Publisher Copyright:
© 2019 Spandidos Publications. All rights reserved.
Keywords
- apoptosis
- colorectal cancer
- microRNA
- microRNA-5191
- ribosomal protein S6 kinase β1
ASJC Scopus subject areas
- Oncology
- Cancer Research