Silencing of circRERE(4-5) inhibits ONECUT2-mediated tumorigenesis and metastasis in gastric cancer

TL;DR

This study shows that a specific circular RNA, circRERE(4-5), promotes gastric cancer growth and spread, and targeting it could be a new treatment strategy.

Contribution

The study identifies circRERE(4-5) as a novel driver of gastric cancer progression and metastasis, and demonstrates its therapeutic potential.

Findings

circRERE(4-5) is significantly upregulated in gastric cancer tissues and cells.

Knockdown of circRERE(4-5) inhibits cancer cell growth and metastasis via the miR-571 and ONECUT2 pathway.

Antisense oligonucleotides targeting circRERE(4-5) reduce tumor growth and spread in mouse models.

Abstract

The leading cause of mortality for gastric cancer (GC) patients is metastasis. Investigating the mechanisms that drive the dissemination of GC could reveal crucial aspects of tumour biology and potentially lead to valuable therapeutic strategies. Circular RNAs (circRNAs), which are extensively expressed in tumours, are involved in a range of biological processes, such as cancer metastasis and cancer immunity. In the present study, the role of circRNAs in the progression and dissemination of GC was investigated.

CircRNAs expression were analyzed using GEO datasets and qRT-PCR. The role of circRNAs in the progression of GC was investigated using functional assays, molecular experiments, and in vivo xenograft models.

We identified a circRNA, circRERE(4-5) (circBase ID: hsa_circ_0009594), which facilitated GC progression. CircRERE(4-5) was notably elevated in GC tissues and cells, and plasma circRERE(4-5) levels correlated closely with GC size and metastasis. Knockdown of circRERE(4-5) suppressed the growth and movement of GC cells through a pathway involving miR-571 and one cut homeobox 2 (ONECUT2). Moreover, antisense oligonucleotides targeting circRERE(4-5) suppressed the growth and spread of xenograft tumours in mice.

Our research uncovers the functional and diagnostic significance of circRERE(4–5) and highlights circRNAs as pivotal factors in GC development and spread.

Figures