Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells
Micro-RNA-21 (miR-21) is a vital regulator of colorectal cancer (CRC) progression and has emerged as a potential therapeutic target in CRC treatment. Our study using real-time PCR assay found that a secondary bile acid, lithocholic acid (LCA), stimulated the expression of miR21 in the CRC cell lines...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10209 |
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| author | Thinh-Thi Nguyen Thuan-Trong Ung Shinan Li Dhiraj Kumar Sah Sun-Young Park Sen Lian Young-Do Jung |
| author_facet | Thinh-Thi Nguyen Thuan-Trong Ung Shinan Li Dhiraj Kumar Sah Sun-Young Park Sen Lian Young-Do Jung |
| author_sort | Thinh-Thi Nguyen |
| collection | DOAJ |
| description | Micro-RNA-21 (miR-21) is a vital regulator of colorectal cancer (CRC) progression and has emerged as a potential therapeutic target in CRC treatment. Our study using real-time PCR assay found that a secondary bile acid, lithocholic acid (LCA), stimulated the expression of miR21 in the CRC cell lines. Promoter activity assay showed that LCA strongly stimulated miR21 promoter activity in HCT116 cells in a time- and dose-dependent manner. Studies of chemical inhibitors and miR21 promoter mutants indicated that Erk1/2 signaling, AP-1 transcription factor, and STAT3 are major signals involved in the mechanism of LCA-induced miR21 in HCT116 cells. The elevation of miR21 expression was upstream of the phosphatase and tensin homolog (PTEN) inhibition, and CRC cell proliferation enhancement that was shown to be possibly mediated by PI3K/AKT signaling activation. This study is the first to report that LCA affects miR21 expression in CRC cells, providing us with a better understanding of the cancer-promoting mechanism of bile acids that have been described as the very first promoters of CRC progression. |
| first_indexed | 2024-03-10T07:00:38Z |
| format | Article |
| id | doaj.art-3e32388975694305ac4e9a6e049cced0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:38Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3e32388975694305ac4e9a6e049cced02023-11-22T16:06:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191020910.3390/ijms221910209Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer CellsThinh-Thi Nguyen0Thuan-Trong Ung1Shinan Li2Dhiraj Kumar Sah3Sun-Young Park4Sen Lian5Young-Do Jung6Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaResearch Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaResearch Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaResearch Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaResearch Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaResearch Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaMicro-RNA-21 (miR-21) is a vital regulator of colorectal cancer (CRC) progression and has emerged as a potential therapeutic target in CRC treatment. Our study using real-time PCR assay found that a secondary bile acid, lithocholic acid (LCA), stimulated the expression of miR21 in the CRC cell lines. Promoter activity assay showed that LCA strongly stimulated miR21 promoter activity in HCT116 cells in a time- and dose-dependent manner. Studies of chemical inhibitors and miR21 promoter mutants indicated that Erk1/2 signaling, AP-1 transcription factor, and STAT3 are major signals involved in the mechanism of LCA-induced miR21 in HCT116 cells. The elevation of miR21 expression was upstream of the phosphatase and tensin homolog (PTEN) inhibition, and CRC cell proliferation enhancement that was shown to be possibly mediated by PI3K/AKT signaling activation. This study is the first to report that LCA affects miR21 expression in CRC cells, providing us with a better understanding of the cancer-promoting mechanism of bile acids that have been described as the very first promoters of CRC progression.https://www.mdpi.com/1422-0067/22/19/10209miR21lithocholic acidcolorectal cancerSTAT3PTEN |
| spellingShingle | Thinh-Thi Nguyen Thuan-Trong Ung Shinan Li Dhiraj Kumar Sah Sun-Young Park Sen Lian Young-Do Jung Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells International Journal of Molecular Sciences miR21 lithocholic acid colorectal cancer STAT3 PTEN |
| title | Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells |
| title_full | Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells |
| title_fullStr | Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells |
| title_full_unstemmed | Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells |
| title_short | Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells |
| title_sort | lithocholic acid induces mir21 promoting pten inhibition via stat3 and erk 1 2 signaling in colorectal cancer cells |
| topic | miR21 lithocholic acid colorectal cancer STAT3 PTEN |
| url | https://www.mdpi.com/1422-0067/22/19/10209 |
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