Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar;72(3):426-439.
doi: 10.1002/iub.2202. Epub 2019 Nov 28.

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR-149-5p/IL-6/STAT3 pathway

Zhiqiao Xu  1 , Xiaojing Tie  1 , Ning Li  1 , Zhenying Yi  1 , Fengqian Shen  1 , Yan Zhang  1
Affiliations

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR-149-5p/IL-6/STAT3 pathway

Zhiqiao Xu et al. IUBMB Life. 2020 Mar.

Abstract

Circular RNAs (circRNAs) are novel noncoding RNAs (ncRNAs) with covalently closed-loop structures that play an essential regulatory role in diverse malignancies, including esophageal squamous cell cancer (ESCC). Circ_0000654 expression in ESCC and its mechanism of action remains unclear. Real-time PCR (RT-PCR) was employed to detect circ_0000654 and miR-149-5p expression in ESCC tissues. Circ_0000654 and miR-149-5p expression in ESCC cells was selectively regulated. Furthermore, interleukin 6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) expression in cells was detected by RT-PCR and western blot analysis, while CCK8, BrdU, flow cytometry, and transwell assays were used to monitor cell proliferation, apoptosis, migration and invasion, respectively. The dual-luciferase reporter assay and RIP assay were used to verify the targeting relationship between circ_0000654 and miR-149-5p, miR-149-5p and IL-6. The function of circ_0000654 on ESCC cell proliferation and metastasis in vivo was examined using a subcutaneous xenograft model and a tail intravenous injection model in nude mice. Circ_0000654 was significantly upregulated in ESCC tissues and cell lines, and its high expression was remarkably associated with an increased T stage and local lymph node metastasis in ESCC patients. Circ_0000654 overexpression and knockdown experiments revealed that circ_0000654 regulated ESCC cell proliferation, migration, invasion, and apoptosis in vitro. Circ_0000654 was identified as a sponge of miR-149-5p and facilitated ESCC progression by indirectly activating the IL-6/STAT3 signaling pathway. Additionally, knocking down circ_0000654 strikingly repressed ESCC growth and metastasis in vivo. In summary, circ_0000654 functions as an oncogenic circRNA in ESCC and accelerates ESCC progression via adsorbing miR-149-5p and activating the IL-6/STAT3 signaling pathway.

Keywords: ESCC; IL-6; STAT3; circ_0000654; miR-149-5p.

PubMed Disclaimer

References

REFERENCES

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2019;69(1):7-34.
    1. Ko JM, Ning L, Zhao XK, et al. BRCA2 loss-of-function germline mutations are associated with esophageal squamous cell carcinoma risk in Chinese. Int J Cancer. 2019. https://doi.org/10.1002/ijc.32619.
    1. Lin L, Lin DC. Biological significance of tumor heterogeneity in esophageal squamous cell carcinoma. Cancers (Basel). 2019; 11 (8). pii: E1156
    1. Shen FF, Pan Y, Yang HJ, et al. Decreased expression of SPINT1-AS1 and SPINT1 mRNA might be independent Unfavorable prognostic indicators in esophageal squamous cell carcinoma. Onco Targets Ther. 2019;12:4755-4763.
    1. Cao S, Chen G, Yan L, Li L, Huang X. Contribution of dysregulated circRNA_100876 to proliferation and metastasis of esophageal squamous cell carcinoma. Onco Targets Ther. 2018;11:7385-7394.

MeSH terms