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环状 RNA circHIPK3 介导的肺癌细胞对吉非替尼耐药的机制研究。

Mechanism of RNA circHIPK3 Involved in Resistance of Lung Cancer Cells to Gefitinib.

机构信息

Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.

出版信息

Biomed Res Int. 2022 Apr 19;2022:4541918. doi: 10.1155/2022/4541918. eCollection 2022.

DOI:10.1155/2022/4541918
PMID:35496045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9042616/
Abstract

To study the mechanism of circular ribonucleic acid (RNA) circHIPK3 involved in the resistance of lung cancer cells to gefitinib, 110 patients with lung cancer were recruited as the research objects, and the tumor tissue and para-cancerous tissue of each patient's surgical specimens were collected and paraffinized to detect the expression of circHIPK3 in different tissues. Gefitinib drug-resistant cell line of lung cancer was constructed with gefitinib to detect cell apoptosis under different conditions. As a result, the relative expression of circHIPK3 in patients with tumor diameter no less than 3 cm was dramatically inferior to that in patients with tumor diameter less than 3 cm ( < 0.05). The relative expression of circHIPK3 in patients with TNM stage II/III was dramatically inferior to that in patients with tumor, node, and metastasis (TNM) stage I ( < 0.05). Expression of circHIPK3 in patients with lymph node metastasis was dramatically inferior to that in patients without lymph node metastasis ( < 0.05). Of the lung cancer tissues of patients with different TNM stages, only six patients had high expression, and the remaining 104 patients had low expression. Moreover, electrophoresis revealed that circHIPK3 can only be amplified in cDNA, but not in gDNA. Gefitinib-mediated apoptosis rate of lung cancer drug-resistant cell lines decreased notably. In summary, the circular RNA circHIPK3 may have a notably low expression in lung cancer tissues, whose low expression had a certain enhancement effect on the drug resistance of lung adenocarcinoma cells to gefitinib.

摘要

为了研究环状核糖核酸(circRNA)circHIPK3 在肺癌细胞对吉非替尼耐药中的作用机制,招募了 110 名肺癌患者作为研究对象,并收集了每位患者手术标本的肿瘤组织和癌旁组织,对不同组织中 circHIPK3 的表达进行检测。用吉非替尼构建肺癌 gefitinib 耐药细胞系,检测不同条件下细胞凋亡情况。结果显示,肿瘤直径≥3cm 的患者 circHIPK3 的相对表达量明显低于肿瘤直径<3cm 的患者(<0.05)。TNM 分期为 II/III 期的患者 circHIPK3 的相对表达量明显低于 TNM 分期为Ⅰ期的患者(<0.05)。有淋巴结转移的患者 circHIPK3 的表达明显低于无淋巴结转移的患者(<0.05)。在不同 TNM 分期的肺癌组织中,只有 6 例患者高表达,其余 104 例患者低表达。此外,电泳显示,circHIPK3 只能在 cDNA 中被扩增,而在 gDNA 中不能被扩增。吉非替尼介导的肺癌耐药细胞系凋亡率显著降低。综上所述,环状 RNA circHIPK3 在肺癌组织中可能表达明显降低,其低表达对肺腺癌细胞对吉非替尼的耐药性有一定的增强作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/ed831d2ef1c4/BMRI2022-4541918.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/d79dd3055e0d/BMRI2022-4541918.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/818bd2de6071/BMRI2022-4541918.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/90d54c3a1918/BMRI2022-4541918.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/ed831d2ef1c4/BMRI2022-4541918.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/d79dd3055e0d/BMRI2022-4541918.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/8565db3ae910/BMRI2022-4541918.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/a6521b56a97c/BMRI2022-4541918.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/05972a34d201/BMRI2022-4541918.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/1ae5419e77db/BMRI2022-4541918.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/01ad465df855/BMRI2022-4541918.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/818bd2de6071/BMRI2022-4541918.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/90d54c3a1918/BMRI2022-4541918.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/9042616/ed831d2ef1c4/BMRI2022-4541918.009.jpg

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