TY - JOUR
T1 - MiR-5191 functions as a tumor suppressor by targeting RPS6KB1 in colorectal cancer
AU - An, Hyun Ju
AU - Park, Misun
AU - Kim, Joon
AU - Han, Young Hoon
N1 - 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.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - apoptosis
KW - colorectal cancer
KW - microRNA
KW - microRNA-5191
KW - ribosomal protein S6 kinase β1
UR - http://www.scopus.com/inward/record.url?scp=85087220583&partnerID=8YFLogxK
U2 - 10.3892/ijo.2019.4865
DO - 10.3892/ijo.2019.4865
M3 - Article
C2 - 31485593
AN - SCOPUS:85087220583
VL - 55
SP - 960
EP - 972
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 4
ER -