CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1
Summary: CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study sh...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2024-01-01
|
Series: | iScience |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223028067 |
_version_ | 1797372103803011072 |
---|---|
author | Fei Long Buning Tian Liang Li Min Ma Zhijian Chen Guojiang Tan Ning Yin Chonglei Zhong Bowen Yu Yihang Guo Miao Chen Gui Hu |
author_facet | Fei Long Buning Tian Liang Li Min Ma Zhijian Chen Guojiang Tan Ning Yin Chonglei Zhong Bowen Yu Yihang Guo Miao Chen Gui Hu |
author_sort | Fei Long |
collection | DOAJ |
description | Summary: CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study showed circPOFUT1 was highly expressed in CRC tissues and cells. CircPOFUT1 enhanced the proliferation, migration and invasion of CRC cells, and promoted tumor growth and liver metastasis in vivo. It also reinforced stemness and chemoresistance of CRC cells. Mechanistically, circPOFUT1 regulated the function of E2F7 via sponging miR-653-5p, thereby transcriptionally inducing WDR66 expression and further promoting metastasis in CRC. On the other hand, circPOFUT1 promoted stemness and chemoresistance of CRC cells via stabilizing BMI1 in an IGF2BP1-dependent manner. In conclusion, circPOFUT1 fosters CRC metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1. |
first_indexed | 2024-03-08T18:30:04Z |
format | Article |
id | doaj.art-c7ab0054adfc4f6db22df64dc72b29e8 |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-03-08T18:30:04Z |
publishDate | 2024-01-01 |
publisher | Elsevier |
record_format | Article |
series | iScience |
spelling | doaj.art-c7ab0054adfc4f6db22df64dc72b29e82023-12-30T04:44:38ZengElsevieriScience2589-00422024-01-01271108729CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1Fei Long0Buning Tian1Liang Li2Min Ma3Zhijian Chen4Guojiang Tan5Ning Yin6Chonglei Zhong7Bowen Yu8Yihang Guo9Miao Chen10Gui Hu11Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Postdoctoral Station of Basic Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Corresponding authorSummary: CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study showed circPOFUT1 was highly expressed in CRC tissues and cells. CircPOFUT1 enhanced the proliferation, migration and invasion of CRC cells, and promoted tumor growth and liver metastasis in vivo. It also reinforced stemness and chemoresistance of CRC cells. Mechanistically, circPOFUT1 regulated the function of E2F7 via sponging miR-653-5p, thereby transcriptionally inducing WDR66 expression and further promoting metastasis in CRC. On the other hand, circPOFUT1 promoted stemness and chemoresistance of CRC cells via stabilizing BMI1 in an IGF2BP1-dependent manner. In conclusion, circPOFUT1 fosters CRC metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1.http://www.sciencedirect.com/science/article/pii/S2589004223028067CancerCell biologyMolecular biology |
spellingShingle | Fei Long Buning Tian Liang Li Min Ma Zhijian Chen Guojiang Tan Ning Yin Chonglei Zhong Bowen Yu Yihang Guo Miao Chen Gui Hu CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1 iScience Cancer Cell biology Molecular biology |
title | CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1 |
title_full | CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1 |
title_fullStr | CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1 |
title_full_unstemmed | CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1 |
title_short | CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1 |
title_sort | circpofut1 fosters colorectal cancer metastasis and chemoresistance via decoying mir 653 5p e2f7 wdr66 axis and stabilizing bmi1 |
topic | Cancer Cell biology Molecular biology |
url | http://www.sciencedirect.com/science/article/pii/S2589004223028067 |
work_keys_str_mv | AT feilong circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT buningtian circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT liangli circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT minma circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT zhijianchen circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT guojiangtan circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT ningyin circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT chongleizhong circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT bowenyu circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT yihangguo circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT miaochen circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 AT guihu circpofut1fosterscolorectalcancermetastasisandchemoresistanceviadecoyingmir6535pe2f7wdr66axisandstabilizingbmi1 |