circTADA2As suppress breast cancer progression and metastasis via targeting miR-203a-3p/SOCS3 axis

Abstract

More and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.

Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

“…Moreover, circRNAs have been regarded as potential therapeutic targets in breast cancer [6]. Xu et al reported that circRNA transcriptional adaptor 2A (circTADA2A) inhibits cell proliferation, migration and invasion by regulating microRNA-203a-3p/suppressor of cytokine signaling 3 (SOCS3) axis in breast cancer [7]. Furthermore, Zhang et al suggested that circRNA has_ circ_0052112, generated from zinc finger 83, could promote cell migration and invasion by sponging microRNA-125a-5p in breast cancer [8].…”

Upregulation of hsa_circ_0007874 suppresses the progression of ovarian cancer by regulating the miR‐760/SOCS3 pathway

“…miR‐760 downregulation promoted SOCS3 expression. Previous studies validated that SOCS3 expression is downregulated in cancer tissues, including pancreatic cancer, colorectal cancer, lung cancer, bladder cancer, and breast cancer . SOCS3 overexpression has an anti‐proliferative and anti‐metastatic effect in cancer .…”

“…Previous studies validated that SOCS3 expression is downregulated in cancer tissues, including pancreatic cancer, colorectal cancer, lung cancer, bladder cancer, and breast cancer. [32][33][34][35][36] SOCS3 overexpression has an anti-proliferative and anti-metastatic effect in cancer. 37,38 Previous studies have found that when a cytokine or a growth factor binds to an intracellular receptor as a ligand, the receptor can form a heterodimer and phosphorylate the JAK kinase.…”

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

“…For instance, circTADA2A-E6 could sponge miR-203a-3p to reduce the expression of miR-203a-3p; thereby restoring the expression of suppressor of cytokine signaling 3 (SOCS3), a target gene of miR-203a-3p, resulting in suppressed the progression and metastasis of BC. 68 In addition, circKIF4A promoted proliferation and migration of triplenegative breast cancer (TNBC), cells by directly sponging miR-375 to relieve the suppression of KIF4A target gene. 69 Moreover, more circRNAs, such as circPLK1, circ-UBE2D2, circBMPR2, circ_0025202, circ_0103552, circ_0072309, circ_001783, involved in the occurrence and development of BC by acting as miRNA sponge have been reported.…”