He Yuanqiang, Li Gang, Fu Ran, Li Yue, Wang Ying
Department of Respiratory and Critical Care Medicine, Huai'an Second People's Hospital, the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an City, China.
Biomol Biomed. 2025 Mar 7;25(4):940-953. doi: 10.17305/bb.2024.11140.
Circular RNA (circRNA) has been proven to be a key regulator in a range of tumor illnesses, such as lung adenocarcinoma (LUAD); however, the regulatory mechanisms of circRNA remain unclear. In this study, circRNA (hsa_circ_0001492) in LUAD was examined for its regulatory and functional potential. qRT-PCR was used to assess the hsa_circ_0001492 level in LUAD. The RNAse R digestion test was employed to isolate hsa_circ_0001492. The primary location of hsa_circ_0001492 enrichment in LUAD cells was identified through a nucleoplasmic separation test. LUAD cell migration, proliferation, and spherogenicity were examined using wound healing, transwell, EdU, and cell spherogenicity assays. The association between miR-145-5p and hsa_circ_0001492/ovarian carcinoma immunoreactive antigen domain 2 (OCIAD2) was validated using a dual luciferase experiment. The interaction between sh-hsa_circ_0001492 and miR-145-5p was confirmed through an RNA pull-down assay. The effects of hsa_circ_0001492, miR-145-5p, and OCIAD2 on LUAD tumor development were examined using xenograft mouse models and immunohistochemistry tests. Results showed a higher amount of hsa_circ_0001492 in LUAD. The cytoplasm of LUAD cells was observed in the area where hsa_circ_0001492 mainly accumulated; hsa_circ_0001492 enhanced LUAD cell migration, proliferation, and sphere-forming ability. MiR-145-5p and OCIAD2 were identified as targets of hsa_circ_0001492 and miR-145-5p, respectively. The level of OCIAD2 was increased by hsa_circ_0001492 through targeted binding to miR-145-5p. In nude mice, tumor growth was inhibited by silencing hsa_circ_0001492, while knockdown of miR-145-5p and overexpression of OCIAD2 promoted the growth of LUAD tumors. In conclusion, hsa_circ_0001492 regulates the hsa-miR-145-5p/OCIAD2 axis to promote the progression of LUAD, and could be a useful target for the diagnosis and treatment of LUAD.
环状RNA（circRNA）已被证明是一系列肿瘤疾病（如肺腺癌，LUAD）中的关键调节因子；然而，circRNA的调节机制仍不清楚。在本研究中，对LUAD中的circRNA（hsa_circ_0001492）的调节和功能潜力进行了研究。采用qRT-PCR评估LUAD中hsa_circ_0001492的水平。采用RNA酶R消化试验分离hsa_circ_0001492。通过核质分离试验确定hsa_circ_0001492在LUAD细胞中富集的主要位置。采用伤口愈合试验、Transwell试验、EdU试验和细胞球形成试验检测LUAD细胞的迁移、增殖和球形成能力。采用双荧光素酶实验验证miR-145-5p与hsa_circ_0001492/卵巢癌免疫反应抗原结构域2（OCIAD2）之间的关联。通过RNA下拉试验证实sh-hsa_circ_0001492与miR-145-5p之间的相互作用。采用异种移植小鼠模型和免疫组织化学试验检测hsa_circ_0001492、miR-145-5p和OCIAD2对LUAD肿瘤发展的影响。结果显示，LUAD中hsa_circ_0001492的含量较高。在hsa_circ_0001492主要积累的区域观察到LUAD细胞的细胞质；hsa_circ_0001492增强了LUAD细胞的迁移、增殖和球形成能力。分别将miR-145-5p和OCIAD2鉴定为hsa_circ_0001492和miR-145-5p的靶标。hsa_circ_0001492通过靶向结合miR-145-5p提高OCIAD2的水平。在裸鼠中，沉默hsa_circ_0001492可抑制肿瘤生长，而敲低miR-145-5p和过表达OCIAD2则促进LUAD肿瘤的生长。总之，hsa_circ_0001492通过调节hsa-miR-145-5p/OCIAD2轴促进LUAD的进展，可能是LUAD诊断和治疗的有用靶点。
