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人环状RNA hsa_circ_0001492通过调控人微小RNA-145-5p/卵巢癌免疫反应抗原结构域2轴促进肺腺癌进展。

Hsa_circ_0001492 regulates the hsa-miR-145-5p/ovarian carcinoma immunoreactive antigen domain 2 axis to promote the progression of lung adenocarcinoma.

作者信息

He Yuanqiang, Li Gang, Fu Ran, Li Yue, Wang Ying

机构信息

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.

出版信息

Biomol Biomed. 2025 Mar 7;25(4):940-953. doi: 10.17305/bb.2024.11140.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a12/11959386/fe2a8cf4c130/bb-2024-11140f1.jpg

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