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Abstract：
BACKGROUND: Long noncoding RNAs (lncRNAs) have been reported to play vital roles in the development and progression of cancer. However, their biological significance and functional mechanisms in non-small cell lung cancer (NSCLC) are mostly unclear.
METHODS: We performed RNA-sequencing to predict the differential expression of lncRNAs in clinical NSCLC and paired paracancerous lung tissues. To identify lncRNA expression, quantitative polymerase chain reaction (qPCR) was used. Using both cell and mouse models, We studied lncRNA AC016727.1\'s function in NSCLC growth and metastasis. Western blot assays, dual luciferase reporter assays, and chromatin immunoprecipitation were used to analyze the functional mechanism of lncRNA AC016727.1.
RESULTS: Our larger NSCLC cohorts validated that the lncRNA AC016727.1 was upregulated in 94 paired NSCLC tissues and correlated with poor survival. Functionally, lncRNA AC016727.1 downregulation inhibited NSCLC cell proliferation, aerobic glycolysis, EMT, and migration, inducing apoptosis. Conversely, upregulated lncRNA AC016727.1 expression exhibited the opposite effect, promoting NSCLC cell survival. Importantly, lncRNA AC016727.1 knockdown inhibited lung cancer growth and slowed the progression of lung metastasis in nude mouse models. Mechanistically, lncRNA AC016727.1 upregulated BACH1 target gene expression by acting as a sponge for miR-98-5p, thereby functioning as a competing endogenous RNA. The function of lncRNA AC016727.1 is mediated by the miR-98-5p/BACH1 axis in NSCLC cells. Meanwhile, the transcription factor HIF-1α can bind to the promoter and activate lncRNA AC016727.1 transcription. lncRNA AC016727.1 regulates HIF-1α expression via BACH1 in NSCLC and forms the lncRNA AC016727.1/BACH1/HIF-1α signaling loop under hypoxic conditions.
CONCLUSIONS: Our study reveals a novel lncRNA AC016727.1/BACH1/HIF-1α signaling loop in the progression of NSCLC under hypoxic conditions, suggesting that lncRNA AC016727.1 could act as a useful biomarker for NSCLC and a new therapeutic target.
METHODS: We performed RNA-sequencing to predict the differential expression of lncRNAs in clinical NSCLC and paired paracancerous lung tissues. To identify lncRNA expression, quantitative polymerase chain reaction (qPCR) was used. Using both cell and mouse models, We studied lncRNA AC016727.1\'s function in NSCLC growth and metastasis. Western blot assays, dual luciferase reporter assays, and chromatin immunoprecipitation were used to analyze the functional mechanism of lncRNA AC016727.1.
RESULTS: Our larger NSCLC cohorts validated that the lncRNA AC016727.1 was upregulated in 94 paired NSCLC tissues and correlated with poor survival. Functionally, lncRNA AC016727.1 downregulation inhibited NSCLC cell proliferation, aerobic glycolysis, EMT, and migration, inducing apoptosis. Conversely, upregulated lncRNA AC016727.1 expression exhibited the opposite effect, promoting NSCLC cell survival. Importantly, lncRNA AC016727.1 knockdown inhibited lung cancer growth and slowed the progression of lung metastasis in nude mouse models. Mechanistically, lncRNA AC016727.1 upregulated BACH1 target gene expression by acting as a sponge for miR-98-5p, thereby functioning as a competing endogenous RNA. The function of lncRNA AC016727.1 is mediated by the miR-98-5p/BACH1 axis in NSCLC cells. Meanwhile, the transcription factor HIF-1α can bind to the promoter and activate lncRNA AC016727.1 transcription. lncRNA AC016727.1 regulates HIF-1α expression via BACH1 in NSCLC and forms the lncRNA AC016727.1/BACH1/HIF-1α signaling loop under hypoxic conditions.
CONCLUSIONS: Our study reveals a novel lncRNA AC016727.1/BACH1/HIF-1α signaling loop in the progression of NSCLC under hypoxic conditions, suggesting that lncRNA AC016727.1 could act as a useful biomarker for NSCLC and a new therapeutic target.
摘要：
背景：据报道，长链非编码RNA（lncRNA）在癌症的发展和进展中起着至关重要的作用。然而,它们在非小细胞肺癌（NSCLC）中的生物学意义和功能机制尚不清楚。
方法：我们进行了RNA测序以预测lncRNAs在临床NSCLC和配对的癌旁肺组织中的差异表达。为了鉴定lncRNA表达，使用定量聚合酶链反应(qPCR)。使用细胞和小鼠模型，我们研究了lncRNAAC016727.1在NSCLC生长和转移中的功能。蛋白质印迹分析,双荧光素酶报告分析，和染色质免疫沉淀用于分析lncRNAAC016727.1的功能机制。
结果：我们更大的NSCLC队列验证了lncRNAAC016727.1在94个配对的NSCLC组织中上调，并与低生存率相关。功能上,lncRNAAC016727.1下调抑制NSCLC细胞增殖，有氧糖酵解，EMT,和移民,诱导细胞凋亡。相反，上调的lncRNAAC016727.1表达表现出相反的效果，促进NSCLC细胞存活。重要的是,在裸鼠模型中，lncRNAAC016727.1敲低抑制肺癌生长并减缓肺转移的进展。机械上,lncRNAAC016727.1通过充当miR-98-5p的海绵上调BACH1靶基因表达，从而起到竞争性内源性RNA的作用。在NSCLC细胞中,lncRNAAC016727.1的功能由miR-98-5p/BACH1轴介导。同时,转录因子HIF-1α可以与启动子结合并激活lncRNAAC016727.1转录。lncRNAAC016727.1在NSCLC中通过BACH1调节HIF-1α表达，并在缺氧条件下形成lncRNAAC016727.1/BACH1/HIF-1α信号环。
结论：我们的研究揭示了在低氧条件下NSCLC进展中的新型lncRNAAC016727.1/BACH1/HIF-1α信号环，这表明lncRNAAC016727.1可以作为NSCLC的有用生物标志物和新的治疗靶点。
方法：我们进行了RNA测序以预测lncRNAs在临床NSCLC和配对的癌旁肺组织中的差异表达。为了鉴定lncRNA表达，使用定量聚合酶链反应(qPCR)。使用细胞和小鼠模型，我们研究了lncRNAAC016727.1在NSCLC生长和转移中的功能。蛋白质印迹分析,双荧光素酶报告分析，和染色质免疫沉淀用于分析lncRNAAC016727.1的功能机制。
结果：我们更大的NSCLC队列验证了lncRNAAC016727.1在94个配对的NSCLC组织中上调，并与低生存率相关。功能上,lncRNAAC016727.1下调抑制NSCLC细胞增殖，有氧糖酵解，EMT,和移民,诱导细胞凋亡。相反，上调的lncRNAAC016727.1表达表现出相反的效果，促进NSCLC细胞存活。重要的是,在裸鼠模型中，lncRNAAC016727.1敲低抑制肺癌生长并减缓肺转移的进展。机械上,lncRNAAC016727.1通过充当miR-98-5p的海绵上调BACH1靶基因表达，从而起到竞争性内源性RNA的作用。在NSCLC细胞中,lncRNAAC016727.1的功能由miR-98-5p/BACH1轴介导。同时,转录因子HIF-1α可以与启动子结合并激活lncRNAAC016727.1转录。lncRNAAC016727.1在NSCLC中通过BACH1调节HIF-1α表达，并在缺氧条件下形成lncRNAAC016727.1/BACH1/HIF-1α信号环。
结论：我们的研究揭示了在低氧条件下NSCLC进展中的新型lncRNAAC016727.1/BACH1/HIF-1α信号环，这表明lncRNAAC016727.1可以作为NSCLC的有用生物标志物和新的治疗靶点。
