Hsa_circ_0005230 is up-regulated and promotes gastric cancer cell invasion and migration via regulating the miR-1299/RHOT1 axis

ABSTRACT

Gastric cancer (GC) is one of the most common cancers in the world. Circular RNAs (circRNAs) are a class of non-coding RNAs that are widely expressed in eukaryotic cells. However, their role has been poorly understood in GC. This report aimed to explore the biological functions of hsa_circ_0005230 and its action mechanism in GC. This study validated that hsa_circ_0005230 was significantly up-regulated in 130 cases of GC tissues using qRT-PCR, and clinicopathological feature analysis revealed that its high expression was positively associated with histological grade, lymph node metastasis, TNM stages, and poor prognosis. In vitro, functional experiments showed that silencing hsa_circ_0005230 significantly decreased GC cell proliferation, invasion and migration capabilities. In addition, the major proteins of EMT (epithelial-mesenchymal transition) relevance have changed. In mechanism studies, bioinformatics analyses were used to predict the hsa_circ_0005230/miR-1299/RHOT1 axis and hsa_circ_0005230 may serve as a sponge for miR-1299 and indirectly regulate the expression of RHOT1. The regulated relationships between the molecules on the axis were verified using qRT-PCR and correlation analysis. Dual-luciferase reporter gene assay has been used to verify the binding site between miR-1299 and RHOT1. WB (Western blotting) and IHC (Immunohistochemical) were used to verify that RHOT1 may play the role of oncoprotein and affect the biological behavior of GC. Overall, hsa_circ_0005230 could enhance the EMT phenotype by promoting RHOT1 expression through sponging miR-1299, thus affecting the biological behavior of GC. Hsa_circ_0005230 can be easily identified as a potential diagnostic biomarker and assessment prognosis target for GC.

Graphical Abstract

KEYWORDS:

• Hsa_circ_0005230
• miR-1299
• RHOT1
• gastric cancer
• migration
• invasion

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Yanyu Peng: Conceptualization, Methodology, Writing-Original draft, Reviewing, Software, Validation.

Dan Sun: Supervision, Data curation, Visualization, and Methodology Reviewing Validation.

Yan Xin: Funding acquisition, Project administration, Resources Supervision, Reviewing, Validation.

Supplementary Material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (No.81071650); Special foundation for Science and Technology Program in Liaoning Province, China (2013225585); and Supporting Project for Climbing Scholars in Liaoning Provincial Universities, China (2009).