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<p>Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. The telomerase RNA component (TERC) is a lncRNA that functions as an essential template for the addition of the telomere repeats; its dysfunctions has been associated with various human diseases. However, how dysregulation of TERC expression and activity affects lung adenocarcinoma (LUAD) progression remains elusive. RNA sequencing (RNA-seq) analysis was used to compare the expression levels of TERC in cancerous and adjacent normal lung tissues. Functional assays of TERC in LUAD cell lines were performed by siRNA-mediated knockdown. Cell proliferation was assessed using the water-soluble tetrazolium salt-1 (WST-1) assay, while colony formation capability was evaluated through colony formation assays. Cell migration and invasion were analyzed using Transwell assays. Reactive oxygen species (ROS) levels were determined by flow cytometry and examined by fluorescence microscopy. The morphology of mitochondria was observed using transmission electron microscopy. Protein expression was analyzed by western blot. The formation of autophagosomes was monitored by fluorescence microscopy following the expression of fluorescently tagged LC3. Xenograft experiments were conducted to test the inhibition of TERC knockdown in LUAD proliferation in vivo. RNA-seq analysis showed that the expression of TERC was upregulated in lung cancer tissues. Silencing TERC suppressed the proliferation, migration, and invasion of lung cancer cells in vitro. Additionally, it inhibited the growth of pulmonary xenografts in mice in vivo. Mechanistic analyses indicated that silencing of TERC increased the expression of autophagy-related proteins LC3B, Beclin-1, and AMP-activated protein kinase (AMPK), while the expression of p62 protein and ferroptosis-regulated proteins GPX4 and SLC7A11 were diminished. Importantly, inhibition of AMPK function counterbalanced the effects of TERC knockdown on autophagy and ferroptosis in LUAD cells. These findings reveal that suppression of TERC in lung cancer promotes autophagy and ferroptosis via regulation of AMPK. They help to understand the mechanism underlying TERC activity in tumorigenesis. It will be of interest to determine the clinical significance of TERC dysregulation in lung cancer.</p>

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Silencing of telomerase RNA component induces autophagy and ferroptosis in A549 and H838 lung cancer cells via AMPK-mediated signaling

  • 期刊论文

  • 发表日期：

    2025年10月14日

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  • Honglian Zhou,
  • Xiaobi Huang,
  • Xiaoyan Cheng,
  • Zijian Liu,
  • Hui Yu,
  • Zhong Huang,
  • Yongyang Chen,
  • Hongyi Liu,
  • Xiaohong Xu,
  • Zhixiong Yang,
  • Wenmei Su

摘要

Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. The telomerase RNA component (TERC) is a lncRNA that functions as an essential template for the addition of the telomere repeats; its dysfunctions has been associated with various human diseases. However, how dysregulation of TERC expression and activity affects lung adenocarcinoma (LUAD) progression remains elusive. RNA sequencing (RNA-seq) analysis was used to compare the expression levels of TERC in cancerous and adjacent normal lung tissues. Functional assays of TERC in LUAD cell lines were performed by siRNA-mediated knockdown. Cell proliferation was assessed using the water-soluble tetrazolium salt-1 (WST-1) assay, while colony formation capability was evaluated through colony formation assays. Cell migration and invasion were analyzed using Transwell assays. Reactive oxygen species (ROS) levels were determined by flow cytometry and examined by fluorescence microscopy. The morphology of mitochondria was observed using transmission electron microscopy. Protein expression was analyzed by western blot. The formation of autophagosomes was monitored by fluorescence microscopy following the expression of fluorescently tagged LC3. Xenograft experiments were conducted to test the inhibition of TERC knockdown in LUAD proliferation in vivo. RNA-seq analysis showed that the expression of TERC was upregulated in lung cancer tissues. Silencing TERC suppressed the proliferation, migration, and invasion of lung cancer cells in vitro. Additionally, it inhibited the growth of pulmonary xenografts in mice in vivo. Mechanistic analyses indicated that silencing of TERC increased the expression of autophagy-related proteins LC3B, Beclin-1, and AMP-activated protein kinase (AMPK), while the expression of p62 protein and ferroptosis-regulated proteins GPX4 and SLC7A11 were diminished. Importantly, inhibition of AMPK function counterbalanced the effects of TERC knockdown on autophagy and ferroptosis in LUAD cells. These findings reveal that suppression of TERC in lung cancer promotes autophagy and ferroptosis via regulation of AMPK. They help to understand the mechanism underlying TERC activity in tumorigenesis. It will be of interest to determine the clinical significance of TERC dysregulation in lung cancer.