CircUBR5 acts as a ceRNA for miR-1179 to up-regulate UBR5 and to promote malignancy of triple-negative breast cancer.

UBR5 is an E3 ubiquitin ligase and an oncogene in a panel of human cancers. However, little is known on its impacts in triple-negative breast cancer (TNBC) and even less on its relationship to circUBR5 (hsa_circ_0001819), a circular RNA derived from exons 2, 3, 4, and 5 of UBR5 gene. In this study, we detected higher expressions of both circUBR5 and UBR5 in TNBC tissues, which were associated with worse prognosis, and also in a panel of breast cancer cells, particularly in TNBC cells. Functionally, circUBR5 was crucial for sustaining the malignant growth and metastasis of TNBC cells both in vitro and in vivo. Mechanistically, the oncogenic phenotypes of circUBC5 were mediated through sponging miR-1179 and up-regulating UBR5. Concomitant silencing circUBR5 and miR-1179 abolished the anti-tumor effects of targeting circUBR5 alone. Therefore, targeting circUBR5/miR-1179/UBR5 axis may benefit the treatment of TNBCs.

Circular RNA circ_0084927 regulates proliferation, apoptosis, and invasion of breast cancer cells via miR-142-3p/ERC1 pathway.

OBJECTIVE: We aimed to investigate the mechanism of circular RNA circ_0084927 in the progression of breast cancer (BC). METHODS: The levels of circ_0084927, miR-142-3p, and ELKS/RAB6-interacting/CAST family member-1 (ERC1) mRNA in the BC tissues and cells were detected by qRT-PCR. CCK8, colony formation, Transwell, and flow cytometry assays were performed to examine the cell proliferation, colony formation, cell invasion, and apoptosis, respectively, in the BC cells with regulated expressions of circ_0084927, miR-142-3p, and ERC1. RNase R treatment was employed to verify the circular structure of circ_0084927. Nucleocytoplasmic separation experiment, bioinformatics analysis, dual-luciferase reporter assay, and RNA immunoprecipitation were performed to investigate the ceRNA mechanism of circ_0084927. RESULTS: High levels of circ_0084927 and ERC1 and low levels of miR-142-3p were detected in the BC tissues and cells. Knockdown of circ_0084927 promoted apoptosis and inhibited proliferation, colony formation, and invasion of BC cells (all P<0.05), whereas overexpression of circ_0084927 in the BC cells achieved the opposite effects. miR-142-3p is the target of circ_0084927. Overexpression of miR-142-3p could inhibit BC cell proliferation, colony formation, and cell invasion and induce apoptosis of the BC cells (all P<0.05), and the effects of miR-142-3p knockout on the BC cells could be reversed by silencing circ_0084927. miR-142-3p could target ERC1. Both ERC1 silencing and circ_0084927 knockout in the BC cells could achieve the tumor-suppressing effect, and this effect could be more remarkable under simultaneous ERC1 silencing and circ_0084927 knockout (all P<0.05). CONCLUSION: Circ_0084927 can promote the progression of BC by regulating the miR-142-3p/ERC1 axis.

LINC01087 is Highly Expressed in Breast Cancer and Regulates the Malignant Behavior of Cancer Cells Through miR-335-5p/Rock1.

PURPOSE: Long non-coding RNA is involved in the genesis and development of various tumors, and it has been found through database screening that LINC01087 is highly expressed in breast cancer (BC), but mechanisms of LINC01087 in BC are still under investigation. Therefore, this study aimed to study relevant mechanisms of LINC01087 in BC to provide potential therapeutic targets for the disease in clinic practice. PATIENTS AND METHODS: The qRT-PCR assay was applied to determine the LINC01087 expression in BC, and the cell counting kit-8 (CCK8) assay, transwell assay, and flow cytometry were used to analyze the proliferation, apoptosis, and invasion of breast cancer cells (BCCs), respectively. The Western blot assay was used to determine the ROCK1 expression, and the luciferase reporter gene assay, RNA-binding protein immunoprecipitation (RIP), and RNA pull-down assays were applied to study the interaction between LINC01087 and miR-335-5p. Moreover, tumor xenotransplantation was conducted in nude mice to explore the effects of LINC01087 on BCCs. RESULTS: The qRT-PCR assay revealed that the LINC01087 expression in BC tissues was higher than that in corresponding tumor-adjacent tissues, and survival analysis revealed an unfavorable prognosis of patients with high expression of LINC01087. Down-regulation of LINC01087 could slow down the proliferation, invasion, and migration of BCCs and accelerate apoptosis of them in vitro. Luciferase reporter gene assay results revealed that LINC01087 enhanced the expression of ROCK1 by regulating miR-335-5p, and LINC01087 could be adopted as a miR-335-5p sponge to inhibit ROCK1 expression. CONCLUSION: LINC01087 is overexpressed in cases with BC, and patients with high expression of it suffer a poor survival. Furthermore, LINC01087 can act as a miR-335-5p sponge to affect the expression of ROCK1 and affect the invasion and migration of BCCs.