失调的环状 RNA 与多发性骨髓瘤的预后密切相关，circ_0026652 通过 microRNA-608 介导的 Wnt/β-catenin 通路预测硼替佐米为基础的治疗反应和生存。
Dysregulated circular RNAs are closely linked to multiple myeloma prognosis, with circ_0026652 predicting bortezomib‑based treatment response and survival via the microRNA‑608‑mediated Wnt/β‑catenin pathway.
机构信息
Department of Hematology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200081, P.R. China.
Department of Hematology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
出版信息
Oncol Rep. 2022 Nov;48(5). doi: 10.3892/or.2022.8410. Epub 2022 Sep 21.
Circular RNA (circRNA/circ) profiles have been suggested to be involved in the prognosis of several types of solid tumors and hematological malignancies, including multiple myeloma (MM). Therefore, the aim of the present study was to comprehensively explore the involvement of circRNA profiles in MM prognosis. A total of 60 patients with MM that underwent bortezomib‑based induction therapy were enrolled. Next, eight patients with complete response (CR) and eight with no response (NR) were randomly selected to detect their circRNA profiles in bone marrow plasma cells (BMPCs) by microarray. Next, 10 candidate circRNAs were verified via reverse transcription‑quantitative PCR (RT‑qPCR) in the BMPCs of 60 patients with MM. Finally, the molecular mechanism of circ_0026652 knockdown underlying the regulation of chemosensitivity to bortezomib was assessed. Microarray showed that 79 circRNAs were upregulated and 167 were downregulated in CR compared with NR cases, which were found to be enriched in carcinogenic and chemoresistance‑related pathways (Wnt, mTOR and MAPK pathways). RT‑qPCR showed that 8/10 circRNAs (circ_0026652, circ_0068708, circ_0088128, circ_0001566, circ_0031113, circ_0083587, circ_0005552 and circ_0007171) were associated with treatment response [CR or objective response rate (ORR)] and 5/10 circRNAs (circ_0026652, circ_0068708, circ_0001566, circ_0031113 and circ_0005552) were associated with progression‑free survival (PFS) or overall survival (OS). Of note, circ_0026652 was a key prognostic marker simultaneously associated with CR, ORR, PFS and OS. Cellular experiments showed that circ_0026652 knockdown enhanced chemosensitivity to bortezomib through the microRNA (miR)‑608‑mediated Wnt/β‑catenin pathway in U266 and RPIM‑8226 cells. In conclusion, dysregulated circRNA profiles were closely associated with MM prognosis, with circ_0026652 being linked to bortezomib‑based treatment response and survival through the miR‑608‑mediated Wnt/β‑catenin pathway.
环状 RNA (circRNA/circ) 谱已被证明参与多种实体瘤和血液恶性肿瘤的预后，包括多发性骨髓瘤 (MM)。因此，本研究的目的是全面探讨 circRNA 谱在 MM 预后中的作用。共纳入 60 例接受硼替佐米为基础的诱导治疗的 MM 患者。然后，随机选择 8 例完全缓解 (CR) 和 8 例无反应 (NR) 的患者，通过微阵列检测其骨髓浆细胞 (BMPC) 中的 circRNA 谱。接下来，通过逆转录-定量 PCR (RT-qPCR) 在 60 例 MM 患者的 BMPC 中验证了 10 个候选 circRNA。最后，评估了 circ_0026652 敲低对硼替佐米化疗敏感性的调节作用。微阵列显示，与 NR 相比，CR 病例中 79 个 circRNA 上调，167 个 circRNA 下调，这些 circRNA 被富集到致癌和化疗耐药相关通路 (Wnt、mTOR 和 MAPK 通路)。RT-qPCR 显示，10 个 circRNA 中的 8 个 (circ_0026652、circ_0068708、circ_0088128、circ_0001566、circ_0031113、circ_0083587、circ_0005552 和 circ_0007171) 与治疗反应 (CR 或客观缓解率 [ORR]) 相关，而 10 个 circRNA 中的 5 个 (circ_0026652、circ_0068708、circ_0001566、circ_0031113 和 circ_0005552) 与无进展生存期 (PFS) 或总生存期 (OS) 相关。值得注意的是，circ_0026652 是一个与 CR、ORR、PFS 和 OS 同时相关的关键预后标志物。细胞实验表明，circ_0026652 通过 U266 和 RPIM-8226 细胞中的 microRNA (miR)-608 介导的 Wnt/β-catenin 通路降低了对硼替佐米的化疗敏感性。总之，失调的 circRNA 谱与 MM 的预后密切相关，circ_0026652 通过 miR-608 介导的 Wnt/β-catenin 通路与硼替佐米为基础的治疗反应和生存相关。
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