Circular RNA circ_0020710 drives tumor progression and immune evasion by regulating the miR-370-3p/CXCL12 axis in melanoma.

Abstract

BACKGROUND:

Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown.

METHODS:

CircRNAs derived from oncogene CD151 were detected and verified by analyzing a large number of melanoma samples through quantitative real-time polymerase chain reaction (qRT-PCR). Melanoma cells were stably transfected with lentiviruses using circ_0020710 interference or overexpression plasmid, and then CCK-8, colony formation, wound healing, transwell invasion assays, and mouse xenograft models were employed to assess the potential role of circ_0020710. RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were used to evaluate the underlying mechanism of circ_0020710.

RESULTS:

Our findings indicated that circ_0020710 was generally overexpressed in melanoma tissues, and high level of circ_0020710 was positively correlated with malignant phenotype and poor prognosis of melanoma patients. Elevated circ_0020710 promoted melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Mechanistically, we found that high level of circ_0020710 could upregulate the CXCL12 expression via sponging miR-370-3p. CXCL12 downregulation could reverse the malignant behavior of melanoma cells conferred by circ_0020710 over expression. Moreover, we also found that elevated circ_0020710 was correlated with cytotoxic lymphocyte exhaustion, and a combination of AMD3100 (the CXCL12/CXCR4 axis inhibitor) and anti-PD-1 significantly attenuated tumor growth.

CONCLUSIONS:

Elevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.

• Authors: Chuan-Yuan Wei, Meng-Xuan Zhu, Nan-Hang Lu, Jia-Qi Liu, Yan-Wen Yang, Yong Zhang, Yue-Dong Shi, Zi-Hao Feng, Jia-Xia Li, Fa-Zhi Qi, Jian-Ying Gu
• Journal: Molecular cancer (Mol Cancer) Vol. 19 Issue 1 Pg. 84 (05 07 2020) ISSN: 1476-4598 [Electronic] England
• PMID: 32381016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CD151 protein, human
• CXCL12 protein, human
• Chemokine CXCL12
• MIRN370 microRNA, human
• MicroRNAs
• RNA, Circular
• Tetraspanin 24

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Case-Control Studies
• Cell Movement
• Cell Proliferation
• Chemokine CXCL12 (genetics, metabolism)
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immune Evasion
• Male
• Melanoma (genetics, immunology, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Invasiveness
• Prognosis
• RNA, Circular (genetics)
• Survival Rate
• Tetraspanin 24 (genetics)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays