Horm Metab Res 2023; 55(12): 876-884
DOI: 10.1055/a-2179-0283
Original Article: Endocrine Research

Hsa_circ_0080608 Attenuates Lung Cancer Progression by Functioning as a Competitive Endogenous RNA to Regulate the miR-661/ADRA1A Pathway

Chengbo Ren
1   Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
,
Ling Cui
1   Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
,
Ruibiao Li
1   Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
,
Xiao Song
1   Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
,
Jinqiu Li
1   Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
,
Qiang Xi
1   Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
,
Zhilin Zhang
1   Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
,
Lixia Zhao
2   Department of Internal Medicine Oncology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
› Author Affiliations
Funding Information The 2022 Medical Science Research Project of Hebei Province — 20220618

Abstract

Circular RNAs (circRNAs) participate in the progression of human cancers and have been broadly elucidated. Here, we aimed to elucidate the roles and functional mechanisms of hsa_circ_0080608 (circ_0080608) in lung cancer. Quantitative real-time PCR (qPCR) was performed to assess the mRNA expression levels of circ_0080608, miR-661, and adrenoceptor alpha 1A (ADRA1A). Western blotting was performed to measure ADRA1A protein levels. CCK-8, colony formation, and Transwell assays were performed to determine the effect of circ_0080608 on cell proliferation and migration. Animal models were used to assess how circ_0080608 influences tumor progression in vivo. The binding relationships of miR-661’s with circ_0080608 and ADRA1A was confirmed using dual-luciferase reporter and RIP assays. Circ_0080608 exhibited relatively low expression in lung cancer samples and cells. Lung cancer cells overexpressing circ_0080608 exhibited reduced migratory and proliferative abilities. Additionally, circ_0080608 binds to miR-661 and operates as a competing endogenous RNA (ceRNA) and shares a miR-661 binding site with the 3’ UTR of ADRA1A. Furthermore, circ_0080608 inversely regulates miR-661 expression, consequently restraining the aggressive behavior of lung cancer cells. Lung cancer cells overexpressing ADRA1A also exhibit repressed migratory and proliferative abilities. However, reintroduction of miR-661 led to a decline in ADRA1A expression, thereby attenuating the functional effects of ADRA1A. Circ_0080608 impedes lung cancer progression by regulating the miR-661/ADRA1A pathway. Our findings provide new insights into the progression of lung cancer.



Publication History

Received: 06 May 2023

Accepted after revision: 11 September 2023

Article published online:
11 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 [Anonymous] Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2020; 70: 313
  • 2 Ribaudo G, Zanforlin E, Zagotto G.. Overcoming resistance in non-small-cell lung cancer: a practical lesson for the medicinal chemist. Arch Pharm (Weinheim) 2018; 351: e1800037
  • 3 Ye R, Tang R, Gan S. et al. New insights into long non-coding RNAs in non-small cell lung cancer. Biomed Pharmacother 2020; 131: 110775
  • 4 Karimpour M, Ravanbakhsh R, Maydanchi M. et al. Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: A review of the literature. Biomed Pharmacother 2021; 143: 112190
  • 5 Ebbesen KK, Hansen TB, Kjems J. Insights into circular RNA biology. RNA Biol 2017; 14: 1035-1045
  • 6 Liu A, Jiang B, Song C. et al. Isoliquiritigenin inhibits circ0030018 to suppress glioma tumorigenesis via the miR-1236/HER2 signaling pathway. MedComm (2020) 2023; 4: e282
  • 7 Zeng Y, Du W, Huang Z. et al. Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205. Cell Death Discov 2023; 9: 153
  • 8 Zhu Z, Wu Q, Zhang M. et al. Hsa_circ_0016760 exacerbates the malignant development of non‑small cell lung cancer by sponging miR‑145‑5p/FGF5. Oncol Rep 2021; 45: 501-512
  • 9 Qi X, Zhang DH, Wu N. et al. ceRNA in cancer: possible functions and clinical implications. J Med Genet 2015; 52: 710-718
  • 10 Dudekula DB, Panda AC, Grammatikakis I. et al. CircInteractome: a web tool for exploring circular RNAs and their interacting proteins and microRNAs. RNA Biol 2016; 13: 34-42
  • 11 Agarwal V, Bell GW, Nam JW. et al. Predicting effective microRNA target sites in mammalian mRNAs. Elife 2015; 4: e05005
  • 12 Liu F, Cai Y, Rong X. et al. MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer. Mol Cancer 2017; 16: 122
  • 13 Zhao W, Liu X.. MiR-3682 promotes the progression of hepatocellular carcinoma (HCC) via inactivating AMPK signaling by targeting ADRA1A. Ann Hepatol 2022; 27 (Suppl. 01) 100570
  • 14 Lei J, Zhu J, Hui B. et al. Circ-HSP90A expedites cell growth, stemness, and immune evasion in non-small cell lung cancer by regulating STAT3 signaling and PD-1/PD-L1 checkpoint. Cancer Immunol Immunother 2023; 72: 101-124
  • 15 Sun JC, Wang L, Zhu XH. et al. Hsa_circ_0006427 suppresses multiplication, migration and invasion of non-small cell lung cancer cells through miR-346/VGLL4 pathway. Cell J 2022; 24: 245-254
  • 16 Xie H, Yao J, Wang Y. et al. Exosome-transmitted circVMP1 facilitates the progression and cisplatin resistance of non-small cell lung cancer by targeting miR-524-5p-METTL3/SOX2 axis. Drug Deliv 2022; 29: 1257-1271
  • 17 Li K, Xu C, Du Y. et al. Comprehensive epigenetic analyses reveal master regulators driving lung metastasis of breast cancer. J Cell Mol Med 2019; 23: 5415-5431
  • 18 Zhu T, Yuan J, Wang Y. et al. MiR-661 contributed to cell proliferation of human ovarian cancer cells by repressing INPP5J expression. Biomed Pharmacother 2015; 75: 123-128
  • 19 Lv F, Zheng K, Yu J. et al. MicroRNA-661 expression is upregulated in pancreatic ductal adenocarcinoma and promotes cell proliferation. Oncol Lett 2018; 16: 6293-6298
  • 20 Wang T, Qin Y, Lai H. et al. The prognostic value of ADRA1 subfamily genes in gastric carcinoma. Oncol Lett 2019; 18: 3150-3158
  • 21 Li C, Chen W, Zhang M. et al. Modulatory effects of Xihuang pill on lung cancer treatment by an integrative approach. Biomed Pharmacother 2020; 130: 110533