Dataset Information

CircREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity.

ABSTRACT: Colorectal cancer (CRC) is one of the most common tumors around the world. Circular RNA is widely involved in tumor progression via unclear mechanisms. Here, circREEP3 is found to be upregulated in CRC tissues. circREEP3 upregulation predicts poor patient survival. circREEP3 knockout suppresses CRC tumorigenesis and metastasis, and impairs stem cell-like phenotype. Mechanistically, circREEP3 recruits the chromatin remodeling protein CHD7 to FKBP10 promoter and activates its transcription. Moreover, circREEP3 restricts RIG-1-dependent antitumor immunity. FKBP10 is highly expressed in CRC tissues and associated with poor prognosis. FKBP10 ectopic expression partially rescues the potential of proliferation and metastasis in circREEP3-deficient CRC cells. Thus, the findings support circREEP3-FKBP10 axis drives CRC progression and may be a critical prognostic marker.

SUBMITTER: Chen Z

PROVIDER: S-EPMC9069384 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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circREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity.

Chen Zhenzhen Z He Luyun L Zhao Liangbo L Zhang Guangtan G Wang Zhiwei Z Zhu Pingping P Liu Benyu B

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20220301 13

Colorectal cancer (CRC) is one of the most common tumors around the world. Circular RNA is widely involved in tumor progression via unclear mechanisms. Here, circREEP3 is found to be upregulated in CRC tissues. circREEP3 upregulation predicts poor patient survival. circREEP3 knockout suppresses CRC tumorigenesis and metastasis, and impairs stem cell-like phenotype. Mechanistically, circREEP3 recruits the chromatin remodeling protein CHD7 to FKBP10 promoter and activates its transcription. Moreov ...[more]

PMID: 35233964

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Project description:BACKGROUND:Liver cancer is one of the most deadly cancers in the world. There are various cells in liver tumor bulk, including liver tumor initiating cells (TICs), which account for liver tumorigenesis, drug resistance, relapse and metastasis. The homeobox (HOX) transcription factors play critical roles in many physiological and pathological processes, while, their roles in liver TICs and liver tumorigenesis remain unknown. METHODS:An unbiased screening was performed using online-available datasets. Liver TICs were sorted by FACS using surface markers CD133, CD13 and EPCAM, or enriched by oncosphere formation assay. TIC self-renewal was examined by oncosphere formation and tumor initiation assay. Loss of function and gain of function assays were performed to examine the role of lncRNA. RNA pulldown, RNA immunoprecipitation, ChIP, Western blot and double FISH were used to explore the molecular mechanism of lncRNA. RESULTS:Here, we examined the expression pattern of HOX transcription factors, and found HOXA10 was overexpressed in liver cancer samples. Moreover, a divergent lncRNA of HOXA10 (termed lncHOXA10 hereafter) was also highly expressed in liver cancer and liver TICs. LncHOXA10 drove liver TIC self-renewal and liver tumorigenesis through HOXA10-dependent manner. LncHOXA10 interacted with SNF2L and recruited NURF chromatin remodeling complex to HOXA10 promoter, and thus initiated the transcription of HOXA10. Through HOXA10 transcriptional regulation, lncHOXA10 activated HOXA10 in liver TICs. LncHOXA10-HOXA10 signaling can be targeted to eliminate liver TICs. Altogether, lncHOXA10 drove HOXA10 expression and thus promoted liver TIC self-renewal. CONCLUSION:HOXA10 was the most highly expressed HOX transcription factor in liver cancer and liver TICs. LncHOXA10 drove the transcriptional activation of HOXA10. This work revealed the important role of HOX transcription factor in liver TIC self-renewal and added a new layer for liver TIC regulation.

Dataset Information

CircREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity.

Publications

circREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity.

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