Deficiency of circ_0103809 Attenuates Non-small Cell Lung Cancer Malignant Progression by Controlling miR-153-3p/HDAC1 Network

Biochem Genet. 2024 Apr;62(2):1160-1181. doi: 10.1007/s10528-023-10470-1. Epub 2023 Aug 10.

Abstract

Circular RNAs are vital players in tumorigenesis. We held the purpose to investigate the role and mechanism of circ_0103809 in non-small cell lung cancer (NSCLC). The expressions of circ_0103809, miR-153-3p and HDAC1 mRNA were determined using quantitative real-time PCR assay, and HDAC1 protein was quantified using western blot analysis. MTT, EdU, flow cytometry, tube-formation, wound healing and tube-formation assays were conducted for functional analysis. The predicted relationship among circ_0103809, miR-153-3p and HDAC1 was ascertained using dual-luciferase analysis, RIP assay and pull-down analysis. Animal models were further constructed to realize circ_0103809's role in vivo. Circ_0103809 was upregulated NSCLC specimens, cells and serum-derived exosomes. Serum exosomal circ_0103809 had the potency to be a diagnostic biomarker for NSCLC. Circ_0103809 silencing inhibited NSCLC cell growth, metastasis and angiogenesis and triggered cell cycle arrest and apoptosis. Circ_0103809 deficiency also suppressed the growth of transplanted tumors. Circ_0103809 acted as the miR-153-3p sponge, and the biological effects of circ_0103809 knockdown were relieved by miR-153-3p inhibition. HDAC1 was directly targeted by miR-153-3p, and miR-153-3p enrichment inhibited NSCLC cell malignant phenotypes by sequestering HDAC1. Circ_0103809 knockdown repressed NSCLC malignant progression partly by regulating miR-153-3p/HDAC1 signaling.

Keywords: Exosome; HDAC1; NSCLC; circ_0103809; miR-153-3p.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics

Substances

  • MicroRNAs