Circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis

Abstract

Circular RNAs (circRNAs) have been shown to play a functional role in a variety of cancers. However, few studies on circRNAs in estrogen receptor-positive breast cancer have been conducted. Here, we investigated the role of circRNA circTP63 in estrogen receptor-positive breast cancer progression and malignant behaviors. First, we observed increased expression of circTP63 in MCF7 cells relative to normal human mammary epithelial cell lines, such as DU4475 and MCF-10A, and the changed oncogenicity of MCF7 cells correlated with circTP63 overexpression and downregulation. Interestingly, a series of gain- and loss-of-function assays revealed that a higher level of FOXM1 was closely associated with MCF7 malignant behaviors induced by circTP63 overexpression. Further investigations showed that circTP63 sponged to miR-873-3p, which targeted FOXM1 mRNA and inhibited its expression. Mechanistically, circTP63 binds to miR-873-3p and prevents the targeting of FOXM1, thus inducing the progression and malignant behaviors of estrogen receptor-positive breast cancer, such as cell proliferation, cell cycle dysregulation, invasion, migration and even tumor growth. CircTP63 might be a potential biomarker or target to treat estrogen receptor-positive breast cancer patients in the future.

CircTP63 Promotes Cell Proliferation and Invasion by Regulating EZH2 via Sponging miR-217 in Gallbladder Cancer

“…Function studies showed circTP63 promotes cell proliferation both in vitro and in vivo by competitively binding to miR-873-3p and regulating the level of FOXM1 [10]. In breast cancer, Deng et al found that circular RNA circTP63 enhances estrogen receptorpositive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis [11]. Our results showed that circTP63 knockdown inhibited cell proliferation and cell cycle progression.…”

“…CircRNAswere found to regulate cell apoptosis, cell proliferation, cell migration and tumor metastasis by regulating gene expression [6].Such as, hsa_circRNA_100269 expression is downregulated in gastric cancer and upregulated hsa_circRNA_100269 inhibits cell growth and tumor metastasis through inactivating PI3K/Akt axis [7].Up-regulated circBACH2 is found in triple-negative breast cancer and contributes to cell proliferation, invasion, and migration of triple-negative breast cancer [8].circCCDC66 expression is upregulated in thyroid cancer and promotes cell proliferation, migratory and invasive abilities and glycolysis through the miR-211-5p/PDK4 axis [9].Hsa_circ_0068515, designated as circTP63, is reported inlung squamous cell carcinoma (LUSC) and correlates with larger tumor size and higher TNM stage in LUSC patients. Besides, upregulated circTP63is also identi ed to promote cell proliferation by functioning as a ceRNA to upregulate FOXM1 in LUSC [10].Another study shows that circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis [11].In hepatocellular carcinoma (HCC), circTP63 is signi cantly upregulated in HCC tissues and cell lines and circTP63 overexpression promotes tumor progression by sponging miR-155-5p and upregulating ZBTB18 expression [12]. However, its role in GBC progression remains unknown.…”

CircTP63 Promotes Cell Proliferation and Invasion by Regulating EZH2 Via Sponging miR-217 in Gallbladder Cancer

“…Function studies showed circTP63 promotes cell proliferation both in vitro and in vivo by competitively binding to miR-873-3p and regulating the level of FOXM1 [10]. In breast cancer, Deng et al found that circular RNA circTP63 enhances estrogen receptorpositive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis [11].…”

“…Besides, upregulated circTP63 is also identi ed to promote cell proliferation by functioning as a ceRNA to upregulate FOXM1 in LUSC [10]. Another study shows that circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis [11]. In hepatocellular carcinoma (HCC), circTP63 is signi cantly upregulated in HCC tissues and cell lines and circTP63 overexpression promotes tumor progression by sponging miR-155-5p and upregulating ZBTB18 expression [12].…”

MiR-873-5p: A Potential Molecular Marker for Cancer Diagnosis and Prognosis

“…Therefore, miR-873-3p targets FOXM1 to inhibit LCA cell proliferation through its cell cycle regulation function ( 159 ). In BC, circTP63 binds to miR-873-3p and prevents its targeted inhibition of FOXM1, thereby inducing the progression and growth of estrogen receptor-positive BC ( 160 ). LINC00941 up-regulates the expression of ATXN2 by competitively binding miR-873-3p, stimulates the proliferation and metastasis of pancreatic adenocarcinoma, and promotes its occurrence and development ( 161 ) ( Figure 8 ).…”