The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis
Abstract Background Recent studies suggest that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. As a newly identified lncRNA, the role of XIST in colorectal cancer (CRC) has not been established. Here, we sought to characterize the role of XIST and its associated regulatory ne...
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| Format: | Article |
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BMC
2020-12-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-020-01647-4 |
| _version_ | 1818350581708750848 |
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| author | Nan Wang Jia-Xing He Guo-Zhan Jia Ke Wang Shuai Zhou Tao Wu Xian-Li He |
| author_facet | Nan Wang Jia-Xing He Guo-Zhan Jia Ke Wang Shuai Zhou Tao Wu Xian-Li He |
| author_sort | Nan Wang |
| collection | DOAJ |
| description | Abstract Background Recent studies suggest that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. As a newly identified lncRNA, the role of XIST in colorectal cancer (CRC) has not been established. Here, we sought to characterize the role of XIST and its associated regulatory network in CRC cells. Methods Expression of XIST mRNA, miR-497-5p, and forkhead box k1 (FOXK1) in CRC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of CRC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between XIST, miR-497-5p, and FOXK1 were predicted and confirmed using a dual-luciferase reporter assay. Expression of FOXK1 protein was quantified by Western blot. Results XIST and FOXK1 expression were significantly upregulated in CRC tissues and cell lines, while miR-497-5p expression was downregulated. XIST knockdown significantly suppressed CRC cell proliferation, migration, and invasion. Silencing of XIST also reversed the downregulation of miR-497-5p and upregulation of FOXK1. Moreover, blocking XIST expression was shown to inhibit CRC tumor growth in vivo and the effects were antagonized by the loss of miR-497-5p. miR-497-5p was shown to act as a sponge of XIST and also targeted FOXK1 in CRC cells. Conclusions XIST was shown to promote the malignancy of CRC cells by competitively binding to miR-497-5p, resulting in an increase in FOXK1 expression. These results suggest that targeting of XIST may represent a possible treatment for CRC. |
| first_indexed | 2024-12-13T18:24:07Z |
| format | Article |
| id | doaj.art-ac6a1239c4274206b36259185acb4844 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-13T18:24:07Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-ac6a1239c4274206b36259185acb48442022-12-21T23:35:38ZengBMCCancer Cell International1475-28672020-12-0120111110.1186/s12935-020-01647-4The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axisNan Wang0Jia-Xing He1Guo-Zhan Jia2Ke Wang3Shuai Zhou4Tao Wu5Xian-Li He6Department of General Surgery, Tangdu Hospital, the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, the Air Force Medical UniversityAbstract Background Recent studies suggest that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. As a newly identified lncRNA, the role of XIST in colorectal cancer (CRC) has not been established. Here, we sought to characterize the role of XIST and its associated regulatory network in CRC cells. Methods Expression of XIST mRNA, miR-497-5p, and forkhead box k1 (FOXK1) in CRC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of CRC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between XIST, miR-497-5p, and FOXK1 were predicted and confirmed using a dual-luciferase reporter assay. Expression of FOXK1 protein was quantified by Western blot. Results XIST and FOXK1 expression were significantly upregulated in CRC tissues and cell lines, while miR-497-5p expression was downregulated. XIST knockdown significantly suppressed CRC cell proliferation, migration, and invasion. Silencing of XIST also reversed the downregulation of miR-497-5p and upregulation of FOXK1. Moreover, blocking XIST expression was shown to inhibit CRC tumor growth in vivo and the effects were antagonized by the loss of miR-497-5p. miR-497-5p was shown to act as a sponge of XIST and also targeted FOXK1 in CRC cells. Conclusions XIST was shown to promote the malignancy of CRC cells by competitively binding to miR-497-5p, resulting in an increase in FOXK1 expression. These results suggest that targeting of XIST may represent a possible treatment for CRC.https://doi.org/10.1186/s12935-020-01647-4LncRNA XISTmiR-497-5pFOXK1Colon cancer cell carcinoma |
| spellingShingle | Nan Wang Jia-Xing He Guo-Zhan Jia Ke Wang Shuai Zhou Tao Wu Xian-Li He The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis Cancer Cell International LncRNA XIST miR-497-5p FOXK1 Colon cancer cell carcinoma |
| title | The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis |
| title_full | The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis |
| title_fullStr | The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis |
| title_full_unstemmed | The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis |
| title_short | The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis |
| title_sort | lncrna xist promotes colorectal cancer cell growth through regulating the mir 497 5p foxk1 axis |
| topic | LncRNA XIST miR-497-5p FOXK1 Colon cancer cell carcinoma |
| url | https://doi.org/10.1186/s12935-020-01647-4 |
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