LncRNA CPS1-IT1 suppresses EMT and metastasis of colorectal cancer by inhibiting hypoxia-induced autophagy through inactivation of HIF-1α

Zhang, Wei; Yuan, Weitang; Song, Junmin; Wang, Shijun; Gu, Xiaoming

doi:10.1016/j.biochi.2017.10.002

Cited by 88 publications

(53 citation statements)

References 31 publications

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“…Autophagy is one of the main regulatory mechanisms of EMT. Long non-coding RNA CPS1-IT may suppress metastasis and EMT by inhibiting hypoxia-induced autophagy through inactivation of hypoxia inducible factor-1α in CRC (14). In the present study levels of several key markers of autophagy were determined, and the results indicated that rhIL-1β inhibited autophagy in CRC, whereas rhIL-1RA activated autophagy.…”

Section: Discussionmentioning

confidence: 52%

Interleukin 1β/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy

et al. 2020

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Interleukin (IL)-1β is a member of the IL-1 family of proteins. IL-1 receptor antagonist (IL-1RA) is an agent that binds to the IL-1 receptor, preventing IL-1 from transmitting signals to cells. The present study aimed to identify the role of the IL-1β/1RA axis in epithelial-mesenchymal transition (EMT), cell invasion, migration, proliferation and clone formation in colorectal cancer (CRC) and to determine its underlying mechanisms of action. Significantly increased expression of both IL-1β and IL-1RA was identified in CRC patient data uploaded in The Cancer Genome Atlas database, and in tumor tissues when compared with matched control tissue. High expression of IL-1β was associated with an increased rate of overall survival and recurrence-free survival. Further research revealed that the IL-1β gene was co-expressed with the IL-1RA gene in tumors of CRC patients. It was additionally determined that recombinant human (rh)IL-1β suppressed autophagy as well as EMT in HCT-116 cells compared with control-treated cells, whereas rhIL-1RA exhibited the opposite effect. In addition, autophagy activator rapamycin (RAPA) rescued the inhibition of EMT in rhIL-1β-treated HCT-116 cells. Moreover, rhIL-1β inhibited cell invasion, migration, proliferation and colony-formation ability, when compared with a control treatment. Compared with a control treatment rhIL-1RA promoted cell invasion, migration, proliferation, but had no effect on clone formation ability. Furthermore, both rhIL-1RA and RAPA rescued inhibition of cell invasion, migration and clone formation ability in rhIL-1β-treated HCT-116 cells. RAPA, but not rhIL-1RA, rescue inhibited proliferation in rhIL-1β-treated HCT-116 cells compared with controls. In addition, it was confirmed that rhIL-1β inhibited the growth of subcutaneous xenografts in nude mice, when compared with control treatments. These results indicated that upregulation of the IL-1β/1RA axis in CRC regulated EMT, cell invasion and migration, proliferation and clone formation via autophagy.

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Section: Discussionmentioning

confidence: 52%

Interleukin 1β/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy

et al. 2020

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“…Expression of the lncRNA CPS1-IT1 is significantly reduced in CRC tissues and cell lines, with in vitro analysis revealing that CPS1-IT1 overexpression suppresses EMT and autophagy by inhibiting HIF-1α activation. The regulation of CRC metastasis by autophagy under hypoxic conditions may therefore be associated with CPS1-IT1 acting as a tumor suppressor [53].…”

Section: Ncrnas Regulate Hif Expression In Crcmentioning

confidence: 99%

“…p70S6K1 [52] lncRNA CPS1-IT1 Inhibits HIF-1α activation and suppresses EMT and autophagy. [53] miR-23a, miR27a, miR-24…”

Section: Mir-210 Mir-21mentioning

confidence: 99%

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

Cho

Han

Hur

et al. 2019

Genes

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Hypoxia-inducible factors (HIFs) are transcription factors that play central roles in cellular responses against hypoxia. In most cancers, HIFs are closely associated with tumorigenesis by regulating cell survival, angiogenesis, metastasis, and adaptation to the hypoxic tumor microenvironment. Recently, non-coding RNAs (ncRNAs) have been reported to play critical roles in the hypoxic response in various cancers. Here, we review the roles of hypoxia-response ncRNAs in gastrointestinal cancer, with a particular focus on microRNAs and long ncRNAs, and discuss the functional relationships and regulatory mechanisms between HIFs and ncRNAs.

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“…18 So far, numerous ncRNAs have been proven to play essential roles in multiple cellular and molecular processes, including migration, invasion, apoptosis, and angiogenesis in the progression of many cancers. 19,20 In CRC, EMT progression can be regulated by many lncRNAs, such as CPS1 intronic transcript 1 (CPS1-IT1), 21 cardiac hypertrophy-related factor, 22 and SLC25A25-AS1. 23 As a newly found tumor-associated lncRNA, zinc finger Ebox binding homeobox 2 antisense RNA 1 (ZEB2-AS1) was demonstrated to be highly expressed in many cancer cells.…”

Section: Introductionmentioning

confidence: 99%

ZEB2-AS1 Accelerates Epithelial/Mesenchymal Transition Through miR-1205/CRKL Pathway in Colorectal Cancer

Jiang

Xie

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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Background: Accumulating reports have demonstrated that long-noncoding RNAs (lncRNAs) play critical roles in the pathological progression of colorectal cancer (CRC). However, the role of lncRNA zinc finger Ebox binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in CRC remains largely unknown. Methods: The authors detected the ZEB2-AS1 expression in CRC tissue sample and CRC cell lines. The effects of ZEB2-AS1 on CRC were identified through in vitro assays (i.e., transwell assay, wound-healing assay, immunofluorescence assay, and Western blot) in a ZEB2-AS1 knockdown system. The molecular mechanism of ZEB2-AS1 was explored via bioinformatic tools, quantitative real-time polymerase chain reaction (qRT-PCR), dual-luciferase reporter assay, RNA immunoprecipitation assay, and so on. Moreover, a series of gain-of-function experiments were performed to identify the effect of ZEB2-AS1 and miR-1205 on epithelial-to-mesenchymal transition (EMT) in CRC cells. Results: This analysis clarified that ZEB2-AS1 was upregulated in both CRC tissue sample and cells lines; meanwhile, the high expression of ZEB2-AS1 was correlated with poor overall survival rate. ZEB2-AS1 knockdown significantly suppresses the EMT in CRC cells. Furthermore, the authors identified that the expression of ZEB2-AS1 was negatively correlated with expression of miR-1205, and CRKL could be a direct target of miR-1205. Through the gain-of-function experiments, they found that ZEB2-AS1 accelerates EMT in CRC cells via modulating the expression of miR-1205 and CRKL. Conclusion: Taken together, this study revealed that ZEB2-AS1 accelerates EMT in CRC through the miR-1205/CRKL pathway, suggesting that ZEB2-AS1 may potentially serve as a target of CRC.

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LncRNA CPS1-IT1 suppresses EMT and metastasis of colorectal cancer by inhibiting hypoxia-induced autophagy through inactivation of HIF-1α

Cited by 88 publications

References 31 publications

Interleukin 1β/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy

Interleukin 1β/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

ZEB2-AS1 Accelerates Epithelial/Mesenchymal Transition Through miR-1205/CRKL Pathway in Colorectal Cancer

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