Hsa_circ_0110757 通过抑制 hsa-miR-1298-5p 而上调 ITGA1 以促进脑胶质瘤对替莫唑胺的耐药性。

Hsa_circ_0110757 upregulates ITGA1 to facilitate temozolomide resistance in glioma by suppressing hsa-miR-1298-5p.

机构信息

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China.

The Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha, 410008, China.

出版信息

Cell Death Dis. 2021 Mar 5;12(3):252. doi: 10.1038/s41419-021-03533-x.

Temozolomide (TMZ) is the internationally recognized and preferred drug for glioma chemotherapy treatment. However, TMZ resistance in glioma appears after long-term use and is an urgent problem that needs to be solved. Circular RNAs (circRNAs) are noncoding RNAs and play an important role in the pathogenesis and progression of tumors. Hsa_circ_0110757 was identified in TMZ-resistant glioma cells by high-throughput sequencing analysis and was derived from reverse splicing of myeloid cell leukemia-1 (Mcl-1) exons. The role of hsa_circ_0110757 in TMZ-resistant glioma was evaluated both in vitro and in vivo. It was found that hsa_circ_0110757 and ITGA1 are more highly expressed in TMZ-resistant glioma than in TMZ-sensitive glioma. The overexpression of hsa_circ_0110757 in glioma patients treated with TMZ was obviously associated with tumor invasion. This study indicates that hsa_circ_0110757 inhibits glioma cell apoptosis by sponging hsa-miR-1298-5p to promote ITGA1 expression. Thus, hsa_circ_0110757/hsa-miR-1298-5p/ITGA could be a potential therapeutic target for reversing the resistance of glioma to TMZ.

替莫唑胺（TMZ）是国际公认的、治疗胶质瘤的首选化疗药物。然而，TMZ 耐药性在胶质瘤长期应用后出现，是一个亟待解决的问题。环状 RNA（circRNA）是一类非编码 RNA，在肿瘤的发生和发展中发挥重要作用。高通量测序分析发现，hsa_circ_0110757 来源于髓样细胞白血病-1（Mcl-1）外显子的反向剪接，在 TMZ 耐药性胶质瘤细胞中表达。在体外和体内评估了 hsa_circ_0110757 在 TMZ 耐药性胶质瘤中的作用。结果发现，hsa_circ_0110757 和 ITGA1 在 TMZ 耐药性胶质瘤中的表达明显高于 TMZ 敏感性胶质瘤。在接受 TMZ 治疗的胶质瘤患者中，hsa_circ_0110757 的过表达与肿瘤侵袭明显相关。本研究表明，hsa_circ_0110757 通过海绵吸附 hsa-miR-1298-5p 抑制胶质瘤细胞凋亡，促进 ITGA1 表达。因此，hsa_circ_0110757/hsa-miR-1298-5p/ITGA 可能是逆转胶质瘤 TMZ 耐药性的潜在治疗靶点。