环状 RNA 沉默信息调节因子 1 通过 microRNA-510-5p/SMAD 家族成员 7 轴抑制非小细胞肺癌细胞的恶性表型。

Circular RNA sirtuin-1 restrains the malignant phenotype of non-small cell lung cancer cells via the microRNA-510-5p/SMAD family member 7 axis.

机构信息

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China, BeiJing, 100021, Chin.

Department of Oncology, The Third Medical Center of PLA General Hospital, BeiJing, 100143, China.

出版信息

Acta Biochim Pol. 2023 Oct 18;70(4):855-863. doi: 10.18388/abp.2020_6675.

DOI:10.18388/abp.2020_6675

PMID:37851987

Abstract

Circular RNA (circRNA) sirtuin-1 (SIRT1) is differentially expressed in non-small cell lung cancer (NSCLC), but its specific mechanism is still uncertain. The study was to figure out the latent molecular mechanism of circSIRT1 in NSCLC. The results clarified that circSIRT1 and SMAD family member 7 (SMAD7) were downregulated, but microRNA (miR)-510-5p was upregulated in NSCLC. CircSIRT1 expression was linked with tumor-node-metastasis staging and tumor size in NSCLC patients. Elevating circSIRT1 or suppressing miR-510-5p refrained NSCLC cell activities and glycolysis and inactivated the wnt/β-catenin pathway, while knockdown of circSIRT1 promoted the malignant behavior of NSCLC cells. Besides, inhibition of malignant behavior in NSCLC cells by elevating circSIRT1 was reversed by knockdown of SMDA7. circSIRT1 bound to miR-510-5p to target SMAD7. In short, circSIRT1 represses NSCLC cell malignant development via miR-510-5p to target SMAD7, making it a latent target for NSCLC treatment.

摘要

环状 RNA (circRNA) 沉默信息调节因子 1 (SIRT1) 在非小细胞肺癌 (NSCLC) 中表达差异，但具体机制尚不清楚。本研究旨在探讨 circSIRT1 在 NSCLC 中的潜在分子机制。结果表明，circSIRT1 和 SMAD 家族成员 7 (SMAD7) 在 NSCLC 中下调，而 microRNA (miR)-510-5p 上调。circSIRT1 的表达与 NSCLC 患者的肿瘤-淋巴结-转移分期和肿瘤大小有关。升高 circSIRT1 或抑制 miR-510-5p 可抑制 NSCLC 细胞的活性和糖酵解，并使 wnt/β-catenin 通路失活，而敲低 circSIRT1 则促进 NSCLC 细胞的恶性行为。此外，通过敲低 SMDA7 逆转了升高 circSIRT1 对 NSCLC 细胞恶性行为的抑制作用。circSIRT1 与 miR-510-5p 结合，靶向 SMAD7。总之，circSIRT1 通过 miR-510-5p 靶向 SMAD7 抑制 NSCLC 细胞恶性发展，使其成为 NSCLC 治疗的潜在靶点。