Hsa_circ_0070440 promotes lung adenocarcinoma progression by SLC7A11-mediated-ferroptosis

• Yong Zhao ^[1] ; Qichen Cui ^[1] ; Jian Shen ^[1] ; Weihong Shen ^[1] ; Yuan Weng ^[1]
  1. [1] Jiangnan University

     Jiangnan University

     China

     
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 38, Nº. 12, 2023, págs. 1429-1441
• Idioma: inglés
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• Resumen

  • Background. Circular RNA (circRNA) has recently emerged as having a key role in cancer initiation and progression. A prior study exhibited that hsa_circ_0070440 (circ_0070440) was significantly upregulated in lung cancer cells, but the role and molecular mechanism of circ_0070440 during lung adenocarcinoma (LUAD) development remain unclear.

    Methods. Quantitative real-time polymerase chain reaction (qRT-PCR), Reverse transcription-PCR (RTPCR), RNase R digestion, and Nuclear/cytoplasmic fractionation assay were employed to validate circ_0070440. Proliferation, apoptosis, viability, and ferrous iron level were measured by colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), Annexin V-FITC/PI double staining, Cell Counting Kit-8 (CCK-8), and iron assay in LUAD cells. A xenograft mouse model was used for tumor growth in vivo. Western blot (WB) and immunohistochemistry (IHC) assays were utilized to determine the expression of solute carrier family 7 member 11 (SLC7A11), c-myc, and bcl-xL. The interactions between the circ_0070440/SLC7A11 axis and miR-485-5p were verified by RNA pull-down assay and dual-luciferase reporter assay.

    Results. Circ_0070440 was significantly upregulated in LUAD cells. Knockdown of circ_0070440 inhibited growth and promoted both apoptosis and ferroptosis of LUAD cells. Moreover, our results showed that circ_0070440 contributed to malignant progression and suppressed ferroptosis of LUAD by sponging miR485-5p and upregulating SLC7A11 expression.

    Furthermore, circ_0070440 and SLC7A11 levels were up-regulated, and the miR-485-5p level was more downregulated in the tumor tissues than in normal tissues of LUAD patients.

    Conclusion. Circ_0070440 modulated LUAD malignant progression and ferroptosis via targeting SLC7A11, implying a significant role of the circ_0070440/miR-485-5p/SLC7A11 axis in the diagnosis and treatment of LUAD.