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<p>Cisplatin resistance significantly limits chemotherapy options and leads to a poor prognosis in patients with lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators of drug resistance mechanisms in various tumors. In this study, we investigated the role and underlying molecular mechanism of the focally amplified lncRNA on chromosome 1 (<i>FAL1</i>) in LUAD cisplatin resistance. <i>FAL1</i> expression levels were measured in blood samples from LUAD patients receiving cisplatin-based chemotherapy and in cisplatin-resistant LUAD cell lines. The functional roles of <i>FAL1</i> in modulating cisplatin-induced apoptosis and protective autophagy were evaluated using colony formation, flow cytometry, and autophagic flux monitoring assays. Additionally, a xenograft mouse model was employed to assess tumor growth and chemoresistance <i>in vivo</i>. We found that <i>FAL1</i> levels were significantly elevated in the serum of patients with cisplatin-resistant LUAD and in resistant cell lines. <i>FAL1</i> knockdown markedly decreased cell proliferation, increased cisplatin-induced apoptosis, and attenuated autophagic flux. Conversely, <i>FAL1</i> overexpression promoted cell survival and hyperactivated autophagy under cisplatin treatment. Mechanistically, <i>FAL1</i> stabilized BMI1, leading to the direct transcriptional repression of the pro-apoptotic and autophagy-regulating gene, BCL2-like 11 (<i>BCL2L11/BIM</i>). <i>In vivo</i> experiments confirmed that <i>FAL1</i> overexpression promoted cisplatin resistance in xenografts via the BMI1/BIM pathway. Taken together, our study demonstrates that <i>FAL1</i> drives cisplatin resistance in LUAD by shifting the balance between apoptosis and autophagy through the BMI1/BIM axis. These findings highlight <i>FAL1</i> as a promising therapeutic target to overcome cisplatin resistance in LUAD.</p>

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FAL1 facilitates cisplatin resistance of lung adenocarcinoma via BMI1/BIM-mediated apoptosis–autophagy interaction

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Teng Ma,
  • Yang Xia,
  • Yijiang Chen,
  • Han Lin,
  • Chunfeng Pan

摘要

Cisplatin resistance significantly limits chemotherapy options and leads to a poor prognosis in patients with lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators of drug resistance mechanisms in various tumors. In this study, we investigated the role and underlying molecular mechanism of the focally amplified lncRNA on chromosome 1 (FAL1) in LUAD cisplatin resistance. FAL1 expression levels were measured in blood samples from LUAD patients receiving cisplatin-based chemotherapy and in cisplatin-resistant LUAD cell lines. The functional roles of FAL1 in modulating cisplatin-induced apoptosis and protective autophagy were evaluated using colony formation, flow cytometry, and autophagic flux monitoring assays. Additionally, a xenograft mouse model was employed to assess tumor growth and chemoresistance in vivo. We found that FAL1 levels were significantly elevated in the serum of patients with cisplatin-resistant LUAD and in resistant cell lines. FAL1 knockdown markedly decreased cell proliferation, increased cisplatin-induced apoptosis, and attenuated autophagic flux. Conversely, FAL1 overexpression promoted cell survival and hyperactivated autophagy under cisplatin treatment. Mechanistically, FAL1 stabilized BMI1, leading to the direct transcriptional repression of the pro-apoptotic and autophagy-regulating gene, BCL2-like 11 (BCL2L11/BIM). In vivo experiments confirmed that FAL1 overexpression promoted cisplatin resistance in xenografts via the BMI1/BIM pathway. Taken together, our study demonstrates that FAL1 drives cisplatin resistance in LUAD by shifting the balance between apoptosis and autophagy through the BMI1/BIM axis. These findings highlight FAL1 as a promising therapeutic target to overcome cisplatin resistance in LUAD.