CircTP63 promotes hepatocellular carcinoma progression by sponging miR-155-5p and upregulating ZBTB18

Abstract

Background: Hepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear.Methods: qRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18.Results: circTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression.Conclusion: Our data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.

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

“…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

“…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.…”