Hsa_circ_0128846 promotes tumorigenesis of colorectal cancer by sponging hsa-miR-1184 and releasing AJUBA and inactivating Hippo/YAP signalling

© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd..

Hsa_circ_0128846 was found to be the most significantly up-regulated circRNA in our bioinformatics analysis. However, the role of hsa_circ_0128846 in colorectal cancer has not been explored. We thus aim to explore the influence and mechanism of hsa_circ_0128846 in colorectal cancer by sponging its downstream miRNA target miR-1184. We collected 40 colorectal cancer patients' tumour tissues to analyse the expression of hsa_circ_0128846, miR-1184 and AJUBA using qRT-PCR and Western blot where needed. Then, we constructed stably transfected SW480 and HCT116 cells to study the influence of hsa_circ_0128846, miR-1184 and AJUBA on colorectal cancer cell phenotypes. To obtain reliable results, a plethora of experiments including RNA immunoprecipitation assay, flow cytometry, EdU incorporation assay, wound healing migration assay, transwell invasion assay and live imaging of nude mice xenograft assay were performed. The binding relationship between hsa_circ_0128846, miR-1184 and AJUBA mRNA in colorectal cancer was validated by reported gene assay. In colorectal cancer tissues, circ_0128846 and AJUBA were both significantly up-regulated, while miR-1184 was significantly down-regulated compared with healthy tissues. Meanwhile, hsa_circ_0128846 can absorb miR-1184 to promote the progression of CRC in vivo and SW480 and HCT116 cell phenotypes in vitro. The knockdown of AJUBA, a downstream target of miR-1184, reversed the effect of miR-1184 in CRC cells via enhancing the phosphorylation of the Hippo/YAP signalling pathway proteins MST1, LATS1 and YAP. This study revealed that hsa_circ_0128846 contributed to the development of CRC by decreasing the expression of miR-1184, thereby increasing AJUBA expression and inactivating Hippo/YAP signalling.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Journal of cellular and molecular medicine - 24(2020), 17 vom: 11. Sept., Seite 9908-9924

Sprache:

Englisch

Beteiligte Personen:

Wang, Xu [VerfasserIn]
Chen, Yujia [VerfasserIn]
Liu, Wei [VerfasserIn]
Liu, Tao [VerfasserIn]
Sun, Di [VerfasserIn]

Links:

Volltext

Themen:

AJUBA
AJUBA protein, human
Cell Cycle Proteins
Circ_0128846
Colorectal cancer
EC 2.7.11.1
Hippo
Journal Article
LIM Domain Proteins
MIRN1184 microRNA, human
MiR-1184
MicroRNAs
Protein Serine-Threonine Kinases
RNA, Circular
Transcription Factors
YAP signalling pathway
YY1AP1 protein, human

Anmerkungen:

Date Completed 13.09.2021

Date Revised 04.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/jcmm.15590

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312579047