Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells
Human INO80 chromatin remodeling complex (INO80 complex) as a transcription cofactor is widely involved in gene transcription regulation and is frequently highly expressed in tumor cells. However, few reports exist on the mutual regulatory mechanism between INO80 complex and non-coding microRNAs. He...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10685 |
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| author | Junaid Ali Shah Yujuan Miao Jinmeng Chu Wenqi Chen Qingzhi Zhao Chengyu Cai Saadullah Khattak Fei Wang Jingji Jin |
| author_facet | Junaid Ali Shah Yujuan Miao Jinmeng Chu Wenqi Chen Qingzhi Zhao Chengyu Cai Saadullah Khattak Fei Wang Jingji Jin |
| author_sort | Junaid Ali Shah |
| collection | DOAJ |
| description | Human INO80 chromatin remodeling complex (INO80 complex) as a transcription cofactor is widely involved in gene transcription regulation and is frequently highly expressed in tumor cells. However, few reports exist on the mutual regulatory mechanism between INO80 complex and non-coding microRNAs. Herein, we showed evidence that the INO80 complex transcriptionally controls microRNA-372 (miR-372) expression through RNA-Seq analysis and a series of biological experiments. Knocking down multiple subunits in the INO80 complex, including the <i>INO80</i> catalytic subunit, <i>YY1</i>, <i>Ies2</i>, and <i>Arp8</i>, can significantly increase the expression level of miR-372. Interestingly, mimicking miR-372 expression in HCT116 cells, in turn, post-transcriptionally suppressed INO80 and Arp8 expression at both mRNA and protein levels, indicating the existence of a mutual regulatory mechanism between the INO80 complex and miR-372. The target relationship between miR-372 and INO80 complex was verified using luciferase assays in HCT116 colon cancer cells. As expected, miR-372 mimics significantly suppressed the luciferase activity of pMIR-luc/INO80 and pMIR-luc/Arp8 3′-UTR in cells. In contrast, the miR-372 target sites in the 3′-UTRs linked to the luciferase reporter were mutagenized, and both mutant sites lost their response to miR-372. Furthermore, the mutual modulation between the INO80 complex and miR-372 was involved in cell proliferation and the p53/p21 signaling pathway, suggesting the synergistic anti-tumor role of the INO80 complex and miR372. Our results will provide a solid theoretical basis for exploring miR-372 as a biological marker of tumorigenesis. |
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| language | English |
| last_indexed | 2024-03-11T01:40:05Z |
| publishDate | 2023-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-72d5e24b44c84cb3937bc550d317f0782023-11-18T16:41:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131068510.3390/ijms241310685Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 CellsJunaid Ali Shah0Yujuan Miao1Jinmeng Chu2Wenqi Chen3Qingzhi Zhao4Chengyu Cai5Saadullah Khattak6Fei Wang7Jingji Jin8School of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaHenan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaHuman INO80 chromatin remodeling complex (INO80 complex) as a transcription cofactor is widely involved in gene transcription regulation and is frequently highly expressed in tumor cells. However, few reports exist on the mutual regulatory mechanism between INO80 complex and non-coding microRNAs. Herein, we showed evidence that the INO80 complex transcriptionally controls microRNA-372 (miR-372) expression through RNA-Seq analysis and a series of biological experiments. Knocking down multiple subunits in the INO80 complex, including the <i>INO80</i> catalytic subunit, <i>YY1</i>, <i>Ies2</i>, and <i>Arp8</i>, can significantly increase the expression level of miR-372. Interestingly, mimicking miR-372 expression in HCT116 cells, in turn, post-transcriptionally suppressed INO80 and Arp8 expression at both mRNA and protein levels, indicating the existence of a mutual regulatory mechanism between the INO80 complex and miR-372. The target relationship between miR-372 and INO80 complex was verified using luciferase assays in HCT116 colon cancer cells. As expected, miR-372 mimics significantly suppressed the luciferase activity of pMIR-luc/INO80 and pMIR-luc/Arp8 3′-UTR in cells. In contrast, the miR-372 target sites in the 3′-UTRs linked to the luciferase reporter were mutagenized, and both mutant sites lost their response to miR-372. Furthermore, the mutual modulation between the INO80 complex and miR-372 was involved in cell proliferation and the p53/p21 signaling pathway, suggesting the synergistic anti-tumor role of the INO80 complex and miR372. Our results will provide a solid theoretical basis for exploring miR-372 as a biological marker of tumorigenesis.https://www.mdpi.com/1422-0067/24/13/10685cancermicroRNAmiR-372-3pINO80 chromatin remodeling complextranscriptional regulation |
| spellingShingle | Junaid Ali Shah Yujuan Miao Jinmeng Chu Wenqi Chen Qingzhi Zhao Chengyu Cai Saadullah Khattak Fei Wang Jingji Jin Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells International Journal of Molecular Sciences cancer microRNA miR-372-3p INO80 chromatin remodeling complex transcriptional regulation |
| title | Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells |
| title_full | Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells |
| title_fullStr | Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells |
| title_full_unstemmed | Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells |
| title_short | Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells |
| title_sort | feedback modulation between human ino80 chromatin remodeling complex and mir 372 in hct116 cells |
| topic | cancer microRNA miR-372-3p INO80 chromatin remodeling complex transcriptional regulation |
| url | https://www.mdpi.com/1422-0067/24/13/10685 |
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