Non-small cell lung cancer (NSCLC) is one of the causes of cancer-related deaths worldwide. Although platinum-based chemotherapy is the main treatment method for advanced patients, acquired resistance often leads to treatment failure. Long non-coding RNAs (lncRNAs) play an important role in tumor occurrence and development, but the specific mechanism of their involvement in chemotherapy resistance in NSCLC is not yet fully understood. This study aims to explore the effect of LINC00641 on the microRNA-1306-5p (miR-1306-5p)/fibroblast growth factor receptor 3 (FGFR3) axis on the malignant progression and chemotherapy resistance of NSCLC cell line H1299. The mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR); and the interaction was verified by the dual-luciferase reporter gene assay. H1299 cells were randomly divided into the following groups: CG group (normal culture), sh-NC group (transfected with sh-NC), sh-LINC00641 group (transfected with sh-LINC00641), sh-LINC00641+anti-NC group (transfected with sh-LINC00641 and anti-NC), sh-LINC00641+anti-miR-1306-5p group (transfected with sh-LINC00641 and anti-miR-1306-5p), mimic-NC group (transfected with mimic-NC), miR-1306-5p-mimics group (transfected with miR-1306-5p-mimics), miR-1306-5p-mimics+OE-NC group (transfected with miR-1306-5p-mimics and OE-NC), and miR-1306-5p-mimics+OE-FGFR3 group (transfected with miR-1306-5p-mimics and OE-FGFR3). Then cell proliferation, migration, and invasion were measured by plate colony formation assay, scratch assay, and Transwell assay, respectively. In addition, H1299/DDP cells were grouped as mentioned above. After that, the chemotherapy resistance of H1299/DDP cells was detected by the MTT method. And Western blot was implemented to detect the protein expressions of FGFR3, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 13 (MMP-13), integrin β1 in H1299 cells, and the P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) in H1299/DDP cells. In NSCLC tissues or cells (H1299, H1299/DDP), LINC00641 and FGFR3 were highly expressed, while miR‑1306‑5p was lowly expressed, and the expression trends of these three factors changed more significantly in the drug‑resistant cell line H1299/DDP (P<0.05). LINC00641 could negatively regulate miR‑1306‑5p in a targeted manner; and miR‑1306‑5p could negatively regulate FGFR3 in a targeted manner. Knockdown of LINC00641 (sh‑LINC00641) or overexpression of miR‑1306‑5p reduced the clone number, scratch healing rate, migration number, invasion number, and the expression of PCNA, MMP‑13, and integrin β1 proteins in H1299 cells (P<0.05), and also suppressed the optical density (OD)540 value and the expression of P‑gp and MRP1 proteins in H1299/DDP cells (P<0.05). In addition, inhibition of miR‑1306‑5p or overexpression of FGFR3 could reverse the inhibitory effects of LINC00641 knockdown or miR‑1306‑5p overexpression on the proliferation, migration, invasion, and chemoresistance of H1299 cells (P<0.05). Knockdown of LINC00641 can regulate the miR-1306-5p/FGFR3 axis, inhibit the malignant progression and chemotherapy resistance of NSCLC cells, and provide a new candidate target for molecular intervention of chemotherapy resistance in NSCLC. 【中文题目：LINC00641调节miR-1306-5p/FGFR3轴
对非小细胞肺癌H1299细胞恶性进展
和化疗耐药性的影响】 【中文摘要：背景与目的 非小细胞肺癌（non-small cell lung cancer, NSCLC）是全球癌症相关死亡的原因之一，尽管以铂类为基础的化疗是晚期患者的主要治疗手段，但获得性耐药常导致治疗失败。长链非编码RNA（long non-coding RNA, lncRNA）在肿瘤发生发展中扮演重要角色，但其在NSCLC化疗耐药中的具体机制尚不完全清楚。本研究旨在探讨LINC00641调节微小RNA-1306-5p（microRNA-1306-5p, miR-1306-5p）/成纤维细胞生长因子受体3（fibroblast growth factor receptor 3, FGFR3）轴对NSCLC细胞H1299恶性进展和化疗耐药性的影响。方法 实时荧光定量聚合酶链式反应（quantitative real-time polymerase chain reaction, qRT-PCR）法检测mRNA表达；双荧光素酶报告基因实验验证互作。将H1299细胞随机分为CG组（正常培养）、sh-NC组（转染sh-NC）、sh-LINC00641组（转染sh-LINC00641）、sh-LINC00641+anti-NC组（转染sh-LINC00641+anti-NC）、sh-LINC00641+anti-miR-1306-5p组（转染sh-LINC00641+anti-miR-1306-5p）、mimic-NC组（转染mimic-NC）、miR-1306-5p-mimics组（转染miR-1306-5p-mimics）、miR-1306-5p-mimics+OE-NC组（转染miR-1306-5p-mimics+OE-NC）、miR-1306-5p-mimics+OE-FGFR3组（转染miR-1306-5p-mimics+OE-FGFR3）。平板克隆形成实验、划痕实验检测细胞迁移，Transwell实验检测细胞迁移和侵袭；另将H1299/DDP细胞按上述进行分组，MTT法检测H1299/DDP细胞化疗耐药性；Western blot检测H1299细胞中FGFR3、增殖细胞核抗原（proliferating cell nuclear antigen, PCNA）、基质金属蛋白酶13（matrix metalloproteinase 13, MMP-13）、整合素β1（integrin β1）以及H1299/DDP细胞中P-糖蛋白（P-glycoprotein, P-gp）、多药耐药相关蛋白1（multidrug resistance-associated protein 1, MRP1）蛋白表达。结果 NSCLC组织或细胞（H1299、H1299/DDP）中LINC00641、FGFR3高表达，miR-1306-5p低表达，且耐药细胞H1299/DDP中3个因子表达趋势变化更明显（P<0.05）。LINC00641可以靶向负调控miR-1306-5p；miR-1306-5p可以靶向负调控FGFR3。敲低sh-LINC00641或过表达miR-1306-5p能够降低H1299细胞克隆数、划痕愈合率、迁移数、侵袭数以及细胞中PCNA、MMP-13、integrin β1蛋白表达（P<0.05），并可以抑制H1299/DDP细胞吸光度（optical density, OD）540值以及细胞中P-gp、MRP1蛋白表达（P<0.05）。抑制miR-1306-5p或过表达FGFR3可逆转敲低sh-LINC00641或过表达miR-1306-5p对H1299细胞增殖、迁移、侵袭和化疗耐药性的抑制作用（P<0.05）。结论 敲低LINC00641可以调节miR-1306-5p/FGFR3轴，抑制NSCLC细胞恶性进展和化疗耐药性，为NSCLC化疗耐药的分子干预提供了新的候选靶点。
】 【中文关键词：肺肿瘤；长链非编码RNA00641；微小RNA-1306-5p；成纤维细胞生长因子受体3；恶性进展；化疗耐药性】.
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arXiv · 2025-02-24
arXiv · 2023-09-06