Dataset Information

Knockdown of circRNA circ_0087378 Represses the Tumorigenesis and Progression of Esophageal Squamous Cell Carcinoma Through Modulating the miR-140-3p/E2F3 Axis.

ABSTRACT:

Background

We aimed to investigate the function and underlying mechanisms of circ_0087378 in esophageal squamous cell carcinoma (ESCC).

Methods

We verified higher circ_0087378 expression in ESCC tissues by performing qRT-PCR assays. We further confirmed the oncogenic roles of circ_0087378 in ESCC cells through a series of biological function assays. Then, we used an RNA pull-down assay and luciferase reporter assay to identify miR-140-3p that directly interacts with circ_0087378. Subsequent studies were performed to demonstrate that the circ_0087378/miR-140-3p/E2F3 axis promotes ESCC development.

Results

We demonstrated that upregulated circ_0087378 expression was positively associated with tumor size, histological grade, tumor stage, the presence of metastasis, and worse survival in patients with ESCC. Our results further revealed that knockdown of circ_0087378 suppressed the proliferation, migration, and invasion of ESCC cells and reduced tumor growth in vivo. Mechanistically, we showed that circ_0087378 could directly bind to miR-miR-140-3p and relieve the suppression for target E2F3, which accelerated cell proliferation, migration, and invasion. Correlation analysis in ESCC specimens supported the involvement of the circ_0087378/miR-140-3p/E2F3 axis in ESCC progression.

Conclusions

This study demonstrated that circ_0087378 might act as a competing endogenous RNA for miR-140-3p, which could inhibit the tumorigenesis and progression of ESCC through upregulating E2F3 expression.

SUBMITTER: Wang J

PROVIDER: S-EPMC7928419 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality. Circular RNAs (CircRNAs) have become a research hotspot in recent years for their vital roles in cancer development and progression. This study aims to clarify the roles of circNTRK2 and its underlying molecular mechanisms in ESCC.MethodsThe levels of circNTRK2, miR-140-3p, and nuclear receptor-interacting protein 1 (NRIP1) mRNA were examined by qRT-PCR. The cell proliferation ability was detected via CCK-8, EdU and colony formation assays. The invasion capacity was tested by using transwell assay. The apoptotic rate was evaluated through flow cytometry. The protein levels of cleaved PARP, cleaved caspase-3, E-cadherin, vimentin, and NRIP1 were measured by western blot assay. The validation of circular structure was performed by Sanger sequencing, divergent primer PCR, and RNase R treatments. The ceRNA regulatory mechanism of circNTRK2 was observed via dual-luciferase reporter, RIP and RNA pull-down assays. The mice xenograft models were constructed to confirm the oncogenicity of circNTRK2 in ESCC in vivo.ResultsCircNTRK2 was highly expressed in ESCC tissues and cells. High expression of circNTRK2 was correlated with advanced TNM stage, lymph node metastasis and short survival. Knockdown of circNTRK2 inhibited ESCC cell proliferation, invasion and epithelial-mesenchymal transition (EMT), and accelerated apoptosis in vitro. Mechanistic assays disclosed that circNTRK2 could act as a sponge for miR-140-3p to abate its suppression on target NRIP1 expression. Moreover, miR-140-3p-induced inhibitory effects on ESCC cell malignant phenotypes were attenuated by the overexpression of circNTRK2. In addition, depletion of NRIP1 impeded cell proliferation, invasion and EMT, while enhanced apoptosis. Furthermore, silencing of circNTRK2 suppressed cell proliferation and invasion through regulating NRIP1 expression. Also, knockdown of circNTRK2 slowed ESCC tumor growth in vivo.ConclusionCircNTRK2 promoted ESCC progression by regulating miR-140-3p/NRIP1 pathway. Our findings contribute to a better understanding of circRNAs as miRNA sponges and highlight a promising therapy target in ESCC.