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Hypoxia-associated circular RNA RPPH1 modulates triple-negative breast cancer cell growth via the miR-1296-5p/TRIM14 axis


Department of Breast Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830011, China

* Address correspondence to: Qian Zhao, email

BIOCELL 2021, 45(3), 671-684.


Hypoxia affects the advancement, metastasis, and metabolism of breast cancer (BC). The circular RNA ribonuclease P RNA component H1 (circRPPH1) (has_circ_0000515) is implicated in tumor progression. Nevertheless, the regulatory mechanism related to circRPPH1 in hypoxia-mediated triple-negative breast cancer (TNBC) progression is indistinct. The expression levels of circRPPH1, miR-1296-5p, tripartite motif-containing 14 (TRIM14) mRNA in tissue samples and cells were examined through quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, migration, and invasion were determined with Cell Counting Kit-8 (CCK-8) or transwell assays. The levels of glucose consumption and lactate production were assessed via the Glucose Assay Kit or Lactate Assay Kit. The protein levels of TRIM14, Glucose Transporter GLUT1 (GLUT1), and lactic dehydrogenase A (LDHA) were detected by western blot analysis. The targeting relationship between circRPPH1 or TRIM14 and miR-1296-5p was verified with dual-luciferase reporter assay. The role of circRPPH1 was confirmed via xenograft assay. We verified that circRPPH1 and TRIM14 expression were increased while miR-1296-5p expression was decreased in BC tissues and hypoxia-cultured TNBC cells. Functionally, circRPPH1 silencing reversed the promoting effect of hypoxia on viability, migration, invasion, and glycolysis of TNBC cells. CircRPPH1 knockdown repressed decreased TNBC cell growth in vivo. Mechanistically, circRPPH1 sponged miR-1296-5p to modulate TRIM14 expression. Also, miR-1296- 5p silencing restored circRPPH1 inhibition-mediated influence on the viability, migration, invasion, and glycolysis of hypoxia-treated TNBC cells. TRIM14 elevation overturned the inhibitory impact of miR-1296-5p mimic on viability, migration, invasion, and glycolysis of hypoxia-cultured TNBC cells. In conclusion, hypoxia-induced circRPPH1 fostered TNBC progression through regulation of the miR-1296-5p/TRIM14 axis, indicating that circRPPH1 was a promising target for TNBC treatment.


Cite This Article

JINSIHAN, D., LI, D., ZHANG, M., FENG, J., ZHAO, Q. (2021). Hypoxia-associated circular RNA RPPH1 modulates triple-negative breast cancer cell growth via the miR-1296-5p/TRIM14 axis. BIOCELL, 45(3), 671–684.

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