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.

The crosstalk between circular RNAs and the tumor microenvironment in cancer metastasis

“…Elevated circ_0020710 was observed in melanoma tissues. It promoted cell proliferation, migration, and invasion in vitro and tumor growth in vivo via the miR-370-3p/CXCL12 axis [114] ( Table 1). The roles of circRNAs in CXCR4/ CXCL12-mediated distant metastasis are depicted in Fig.…”

Circular RNA as a Potential Biomarker for Melanoma: A Systematic Review

“…Red and blue color indicated the oncogenic and suppressive functions of circRNAs in different biological processes involved in melanoma progression, respectively. Up and down arrows indicated the activation and inhibition of physiological processes in melanoma pathogenesis, respectively (Bian et al, 2018 ; Ju et al, 2018 ; Luan et al, 2018 ; Wang Q. et al, 2018 ; Lin et al, 2019 ; Shang et al, 2019 ; Zou et al, 2019 ; Chen J. et al, 2020 ; Chen Z. et al, 2020 ; Hanniford et al, 2020 ; Jin et al, 2020 ; Lu and Li, 2020 ; Lu et al, 2020 ; Qian et al, 2020 ; Tian et al, 2020 ; Wei et al, 2020 ; Liu et al, 2021 ; Yin et al, 2021 ).…”

“…One study showed that mir-144 regulated MAPK signaling pathway factors, such as DUSP5 and TGFBR1 (Qian et al, 2020 ). Other circRNAs which also acted as oncogene and miRNA sponge in melanoma included circ_0025039 (Bian et al, 2018 ), circ_0016418 (Zou et al, 2019 ; Lu et al, 2020 ), circ_0020710 (circ-CD151) (Wei et al, 2020 ), circ_0079593 (Lu and Li, 2020 ), circ_0001591 (Yin et al, 2021 ), and circ_0119872 (Liu et al, 2021 ). Specific miRNA targets and downstream molecules are presented in Table 1 .…”

<p>Clinical Significance of Has_circ_0060937 in Bone Metastasis of NSCLC</p>

“…For example, circRNA circ_0020710 drives tumor progression and immune evasion by regulating the miR-370-3p/CXCL12 axis in melanoma. 8 CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR-8075. 9 CircRNA hsa_circRNA_100290 serves as a ceRNA for miR-378a to regulate oral squamous cell carcinoma cell growth via Glucose transporter-1 (GLUT1) and glycolysis.…”