Wu Zhiqiang, Zeng Xiaofei, Wang Hong, Wang Xianbo
Department of Thoracardiac Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
Department of Thoracic surgery, Ya'an City Second People's Hospital, Ya'an, Sichuan, China.
Cancer Biomark. 2023;38(2):177-189. doi: 10.3233/CBM-220223.
It has been discovered that lncRNA ARAP1-AS1 is upregulated and operates as a tumor promoter in many cancers. However, its pattern of expression and potential mechanism in lung adenocarcinoma (LUAD) is still unknown.
The levels of lncRNA ARAP1-AS1, miR-8068, and CEACAM5 expressions in LUAD cell lines and tissues were assessed by conducting western blot and RT-qPCR analyses. MiR-8068's potential targeting relationships with lncRNA ARAP1-AS1 and CEACAM5 were ascertained by performing bioinformatics analysis. The interaction of lncRNA ARAP1-AS1 with miR-8068 was validated by means of by RIP and luciferase reporter experiments. CCK-8, cell adhesion, and Transwell migration experiments were conducted to study how lncRNA ARAP1-AS1 affects LUAD cell migration, adhesion, and proliferation. To confirm the function of lncRNA ARAP1-AS1 in vivo, a tumor formation experiment was executed.
An elevated expression of lncRNA ARAP1-AS1 was observed among the LUAD cells and tissues. The overexpression of lncRNA ARAP1-AS boosted cell proliferation, adhesion, and migration in LUAD and also favored in vivo tumor growth. MiR-8068 was found to be lncRNA ARAP1-AS1's target gene. MiR-8068 overexpression partially antagonized lncRNA ARAP1-AS1's promotive effect on proliferation, viability, and adhesion. Meanwhile CEACAM5 could alleviate the miR-8068-induced inhibition of tumor growth. The negative correlation of miR-8068 with lncRNA ARAP1-AS1 or CEACAM5 was also revealed.
To upregulate CEACAM5 expression lncRNA ARAP1-AS1 targeted miR-8068, thus promoting the progression of LUAD. This indicates that the lncRNA ARAP1-AS1/miR-8068/CEACAM5 axis has potential as a therapeutic target in LUAD treatment.
已发现长链非编码RNA ARAP1-AS1在多种癌症中表达上调并作为肿瘤促进因子发挥作用。然而，其在肺腺癌（LUAD）中的表达模式和潜在机制仍不清楚。
通过蛋白质免疫印迹法和逆转录-定量聚合酶链反应分析评估LUAD细胞系和组织中长链非编码RNA ARAP1-AS1、miR-8068和癌胚抗原相关细胞黏附分子5（CEACAM5）的表达水平。通过生物信息学分析确定miR-8068与长链非编码RNA ARAP1-AS1和CEACAM5的潜在靶向关系。通过RNA免疫沉淀和荧光素酶报告基因实验验证长链非编码RNA ARAP1-AS1与miR-8068的相互作用。进行细胞计数试剂盒-8、细胞黏附及Transwell迁移实验，以研究长链非编码RNA ARAP1-AS1如何影响LUAD细胞的迁移、黏附和增殖。为了在体内证实长链非编码RNA ARAP1-AS1的功能，进行了肿瘤形成实验。
在LUAD细胞和组织中观察到长链非编码RNA ARAP1-AS1表达升高。长链非编码RNA ARAP1-AS1的过表达促进了LUAD细胞的增殖、黏附和迁移，也有利于体内肿瘤生长。发现miR-8068是长链非编码RNA ARAP1-AS1的靶基因。miR-8068的过表达部分拮抗了长链非编码RNA ARAP1-AS1对增殖、活力和黏附的促进作用。同时，CEACAM5可减轻miR-8068诱导的肿瘤生长抑制。还揭示了miR-8068与长链非编码RNA ARAP1-AS1或CEACAM5的负相关性。
长链非编码RNA ARAP1-AS1靶向miR-8068以上调CEACAM5表达，从而促进LUAD的进展。这表明长链非编码RNA ARAP1-AS1/miR-8068/CEACAM5轴在LUAD治疗中具有作为治疗靶点的潜力。
