与人类多发性骨髓瘤相关的miRNAs表达图谱模型、构建方法及应用技术

本发明专利技术公开了与人类多发性骨髓瘤相关的miRNA表达图谱模型、构建方法及应用，本发明专利技术公开了多发性骨髓瘤患者肿瘤细胞和循环体液miRNAs表达谱，明确了骨髓瘤患者与健康人群之间差异表达miRNAs分子图谱，从中筛选可作为骨髓瘤疾病早期诊断、预后评估、疗效预测的生物学标志物；分析了骨髓瘤细胞特征性miRNAs分子表达图谱，对应靶向调控mRNA；探索了差异miRNA及mRNA分子与骨髓瘤疾病发生进展的相关性及其分子机制。本发明专利技术的miRNAs表达图谱为多发性骨髓瘤的治疗提供了理论依据和实验基础。

Expression pattern model, construction method and application of miRNAs related to human multiple myeloma

【技术实现步骤摘要】
与人类多发性骨髓瘤相关的miRNAs表达图谱模型、构建方法及应用
本专利技术涉及生物
，具体是一种与人类多发性骨髓瘤相关的miRNA表达图谱模型、构建方法及应用。
技术介绍
目前多发性骨髓瘤(MultipleMyeloma，MM)最主要、最基本的诊断与预后评价方法都基于骨髓穿刺活检，该检查有一定创伤，老年患者依从性较差，且不能短期反复进行。另外MM发病存在多病灶散在分布的特征，单一位点骨髓穿刺并不能反映患者肿瘤细胞的总体特征，这也成为MM漏诊以及病情评价欠准确的重要原因。因此研发简单易行、创伤性更低的早期诊断、疗效监测及预后评价的生物标志物对于MM临床诊疗有着重要的理论和现实意义。miRNA是一类长度为18-22nt的内源性单链非编码RNA，通过转录后调控mRNA基因表达。现已明确，miRNA分子除参与正常细胞生长、发育、增殖、凋亡外，还在肿瘤的发生发展中起着重要的作用。近年研究发现体液中存在miRNA分子，并且血清miRNA具有肿瘤细胞特异性。由于外周血样本采集容易且可短期、重复获得，有利于临床疾病的追踪观察。同时miRNA还具有稳定性好，不易降解的优点，因此循环miRNA是理想的非侵入性生物标志物，有着重要的应用价值和前景。
技术实现思路
本专利技术为了解决上述的技术问题，而提供一种与人类多发性骨髓瘤相关的miRNAs表达图谱模型、构建方法及应用。本专利技术是按照以下技术方案实现的。一种与人类多发性骨髓瘤相关的miRNA表达图谱模型，与健康对照组相比，多发性骨髓瘤患者浆细胞差异表达miRNAs包括表达上调的hsa-let-7i-5p、hsa-let-7f-5p、hsa-miR-27b-3p、hsa-miR-25-3p、hsa-miR-330-5p、hsa-miR-17-5p、hsa-let-7a-3p、hsa-miR-342-3p、hsa-miR-500a-3p、hsa-let-7d-5p、hsa-miR-20a-5p、hsa-miR-629-5p、hsa-miR-363-3p、hsa-miR-22-3p、hsa-miR-98-5p、hsa-miR-30e-3p、hsa-miR-181a-5p、hsa-miR-106b-3p、hsa-miR-107、hsa-miR-150-5p、hsa-miR-582-3p、hsa-miR-144-3p、hsa-miR-185-5p、hsa-miR-152-3p、hsa-miR-1273d、hsa-miR-101-3p、hsa-miR-30c-5p、hsa-miR-132-3p、hsa-miR-28-5p、hsa-miR-23b-3p、hsa-miR-21-5p、hsa-miR-1291、hsa-miR-26a-5p、hsa-let-7g-5p、hsa-miR-30b-5p、hsa-miR-331-5p、hsa-miR-421、hsa-miR-191-5p、hsa-miR-340-5p、hsa-miR-548az-5p、hsa-miR-652-3p、hsa-miR-148b-3p、hsa-miR-148a-3p、hsa-let-7i-3p、hsa-miR-378c、hsa-miR-454-5p、hsa-miR-141-3p、hsa-miR-15b-3p、hsa-miR-769-5p、hsa-miR-548o-3p、hsa-miR-16-2-3p、hsa-miR-27a-5p、hsa-miR-27b-5p、hsa-miR-3614-5p、hsa-miR-103a-3p、hsa-miR-223-3p、hsa-miR-425-5p、hsa-miR-641、hsa-miR-548d-5p、hsa-miR-23a-3p、hsa-miR-26b-5p、hsa-miR-27a-3p、hsa-miR-18a-3p、hsa-miR-20b-5p、hsa-miR-628-3p、hsa-miR-1303、hsa-miR-4433b-5p、hsa-miR-574-5p、hsa-miR-221-3p、hsa-let-7f-2-3p、hsa-miR-146a-5p、hsa-miR-374b-5p、hsa-miR-210-3p、hsa-miR-30c-1-3p、hsa-miR-30e-5p、hsa-miR-151a-5p、hsa-miR-19a-3p、hsa-miR-93-5p、hsa-miR-142-5p、hsa-miR-425-3p、hsa-miR-576-3p、hsa-miR-339-3p、hsa-miR-874-3p、hsa-miR-140-5p、hsa-miR-548f-3p、hsa-miR-34a-5p、hsa-miR-106a-5p、hsa-miR-642a-3p、hsa-miR-484、hsa-miR-19b-3p、hsa-miR-95-3p、hsa-miR-221-5p、hsa-miR-625-5p、hsa-miR-16-5p、hsa-miR-29a-3p、hsa-miR-1260a、hsa-miR-660-5p、hsa-miR-508-3p、hsa-miR-1260b、hsa-miR-186-5p、hsa-miR-598-3p、hsa-miR-29c-3p、hsa-miR-142-3p、hsa-miR-21-3p、hsa-miR-374a-5p、hsa-miR-22-5p、hsa-miR-374a-3p、hsa-miR-32-5p、hsa-miR-15b-5p、hsa-miR-148a-5p、hsa-miR-29b-3p、hsa-miR-106b-5p、hsa-miR-499a-5p、hsa-miR-148b-5p、hsa-miR-29c-5p、hsa-miR-664a-3p、hsa-miR-130b-5p、hsa-miR-4485、hsa-miR-651-5p、hsa-miR-181a-3p、hsa-miR-365b-3p、hsa-miR-365a-3p、hsa-miR-574-3p、hsa-miR-29b-2-5p、hsa-miR-9-3p、hsa-miR-130b-3p、hsa-miR-331-3p、hsa-miR-454-3p、hsa-miR-15a-5p、hsa-miR-3613-5p、hsa-miR-628-5p、hsa-miR-5701、hsa-miR-335-5p、hsa-miR-4521、hsa-miR-590-3p、hsa-miR-548e-3p、hsa-miR-642a-5p、hsa-miR-1285-3p、hsa-miR-96-5p、hsa-miR-576-5p、hsa-miR-18a-5p、hsa-miR-17-3p、hsa-miR-659-5p、hsa-miR-3687、hsa-miR-514a-3p、hsa-miR-135a-5p、hsa-miR-144-5p、hsa-miR-324-3p、hsa-miR-190b、hsa-miR-1307-5p、hsa-miR-30d-3p、hsa-miR-6516-3p、hsa-miR-3607-3p、hsa本文档来自技高网...

【技术保护点】
1.一种与人类多发性骨髓瘤相关的miRNA表达图谱模型，其特征在于：与健康对照组相比，多发性骨髓瘤患者浆细胞差异表达miRNAs包括表达上调的hsa-let-7i-5p、hsa-let-7f-5p、hsa-miR-27b-3p、hsa-miR-25-3p、hsa-miR-330-5p、hsa-miR-17-5p、hsa-let-7a-3p、hsa-miR-342-3p、hsa-miR-500a-3p、hsa-let-7d-5p、hsa-miR-20a-5p、hsa-miR-629-5p、hsa-miR-363-3p、hsa-miR-22-3p、hsa-miR-98-5p、hsa-miR-30e-3p、hsa-miR-181a-5p、hsa-miR-106b-3p、hsa-miR-107、hsa-miR-150-5p、hsa-miR-582-3p、hsa-miR-144-3p、hsa-miR-185-5p、hsa-miR-152-3p、hsa-miR-1273d、hsa-miR-101-3p、hsa-miR-30c-5p、hsa-miR-132-3p、hsa-miR-28-5p、hsa-miR-23b-3p、hsa-miR-21-5p、hsa-miR-1291、hsa-miR-26a-5p、hsa-let-7g-5p、hsa-miR-30b-5p、hsa-miR-331-5p、hsa-miR-421、hsa-miR-191-5p、hsa-miR-340-5p、hsa-miR-548az-5p、hsa-miR-652-3p、hsa-miR-148b-3p、hsa-miR-148a-3p、hsa-let-7i-3p、hsa-miR-378c、hsa-miR-454-5p、hsa-miR-141-3p、hsa-miR-15b-3p、hsa-miR-769-5p、hsa-miR-548o-3p、hsa-miR-16-2-3p、hsa-miR-27a-5p、hsa-miR-27b-5p、hsa-miR-3614-5p、hsa-miR-103a-3p、hsa-miR-223-3p、hsa-miR-425-5p、hsa-miR-641、hsa-miR-548d-5p、hsa-miR-23a-3p、hsa-miR-26b-5p、hsa-miR-27a-3p、hsa-miR-18a-3p、hsa-miR-20b-5p、hsa-miR-628-3p、hsa-miR-1303、hsa-miR-4433b-5p、hsa-miR-574-5p、hsa-miR-221-3p、hsa-let-7f-2-3p、hsa-miR-146a-5p、hsa-miR-374b-5p、hsa-miR-210-3p、hsa-miR-30c-1-3p、hsa-miR-30e-5p、hsa-miR-151a-5p、hsa-miR-19a-3p、hsa-miR-93-5p、hsa-miR-142-5p、hsa-miR-425-3p、hsa-miR-576-3p、hsa-miR-339-3p、hsa-miR-874-3p、hsa-miR-140-5p、hsa-miR-548f-3p、hsa-miR-34a-5p、hsa-miR-106a-5p、hsa-miR-642a-3p、hsa-miR-484、hsa-miR-19b-3p、hsa-miR-95-3p、hsa-miR-221-5p、hsa-miR-625-5p、hsa-miR-16-5p、hsa-miR-29a-3p、hsa-miR-1260a、hsa-miR-660-5p、hsa-miR-508-3p、hsa-miR-1260b、hsa-miR-186-5p、hsa-miR-598-3p、hsa-miR-29c-3p、hsa-miR-142-3p、hsa-miR-21-3p、hsa-miR-374a-5p、hsa-miR-22-5p、hsa-miR-374a-3p、hsa-miR-32-5p、hsa-miR-15b-5p、hsa-miR-148a-5p、hsa-miR-29b-3p、hsa-miR-106b-5p、hsa-miR-499a-5p、hsa-miR-148b-5p、hsa-miR-29c-5p、hsa-miR-664a-3p、hsa-miR-130b-5p、hsa-miR-4485、hsa-miR-651-5p、hsa-miR-181a-3p、hsa-miR-365b-3p、hsa-miR-365a-3p、hsa-miR-574-3p、hsa-miR-29b-2-5p、hsa-miR-9-3p、hsa-miR-130b-3p、hsa-miR-331-3p、hsa-miR-454-3p、hsa-miR-15a-5p、...

【技术特征摘要】
1.一种与人类多发性骨髓瘤相关的miRNA表达图谱模型，其特征在于：与健康对照组相比，多发性骨髓瘤患者浆细胞差异表达miRNAs包括表达上调的hsa-let-7i-5p、hsa-let-7f-5p、hsa-miR-27b-3p、hsa-miR-25-3p、hsa-miR-330-5p、hsa-miR-17-5p、hsa-let-7a-3p、hsa-miR-342-3p、hsa-miR-500a-3p、hsa-let-7d-5p、hsa-miR-20a-5p、hsa-miR-629-5p、hsa-miR-363-3p、hsa-miR-22-3p、hsa-miR-98-5p、hsa-miR-30e-3p、hsa-miR-181a-5p、hsa-miR-106b-3p、hsa-miR-107、hsa-miR-150-5p、hsa-miR-582-3p、hsa-miR-144-3p、hsa-miR-185-5p、hsa-miR-152-3p、hsa-miR-1273d、hsa-miR-101-3p、hsa-miR-30c-5p、hsa-miR-132-3p、hsa-miR-28-5p、hsa-miR-23b-3p、hsa-miR-21-5p、hsa-miR-1291、hsa-miR-26a-5p、hsa-let-7g-5p、hsa-miR-30b-5p、hsa-miR-331-5p、hsa-miR-421、hsa-miR-191-5p、hsa-miR-340-5p、hsa-miR-548az-5p、hsa-miR-652-3p、hsa-miR-148b-3p、hsa-miR-148a-3p、hsa-let-7i-3p、hsa-miR-378c、hsa-miR-454-5p、hsa-miR-141-3p、hsa-miR-15b-3p、hsa-miR-769-5p、hsa-miR-548o-3p、hsa-miR-16-2-3p、hsa-miR-27a-5p、hsa-miR-27b-5p、hsa-miR-3614-5p、hsa-miR-103a-3p、hsa-miR-223-3p、hsa-miR-425-5p、hsa-miR-641、hsa-miR-548d-5p、hsa-miR-23a-3p、hsa-miR-26b-5p、hsa-miR-27a-3p、hsa-miR-18a-3p、hsa-miR-20b-5p、hsa-miR-628-3p、hsa-miR-1303、hsa-miR-4433b-5p、hsa-miR-574-5p、hsa-miR-221-3p、hsa-let-7f-2-3p、hsa-miR-146a-5p、hsa-miR-374b-5p、hsa-miR-210-3p、hsa-miR-30c-1-3p、hsa-miR-30e-5p、hsa-miR-151a-5p、hsa-miR-19a-3p、hsa-miR-93-5p、hsa-miR-142-5p、hsa-miR-425-3p、hsa-miR-576-3p、hsa-miR-339-3p、hsa-miR-874-3p、hsa-miR-140-5p、hsa-miR-548f-3p、hsa-miR-34a-5p、hsa-miR-106a-5p、hsa-miR-642a-3p、hsa-miR-484、hsa-miR-19b-3p、hsa-miR-95-3p、hsa-miR-221-5p、hsa-miR-625-5p、hsa-miR-16-5p、hsa-miR-29a-3p、hsa-miR-1260a、hsa-miR-660-5p、hsa-miR-508-3p、hsa-miR-1260b、hsa-miR-186-5p、hsa-miR-598-3p、hsa-miR-29c-3p、hsa-miR-142-3p、hsa-miR-21-3p、hsa-miR-374a-5p、hsa-miR-22-5p、hsa-miR-374a-3p、hsa-miR-32-5p、hsa-miR-15b-5p、hsa-miR-148a-5p、hsa-miR-29b-3p、hsa-miR-106b-5p、hsa-miR-499a-5p、hsa-miR-148b-5p、hsa-miR-29c-5p、hsa-miR-664a-3p、hsa-miR-130b-5p、hsa-miR-4485、hsa-miR-651-5p、hsa-miR-181a-3p、hsa-miR-365b-3p、hsa-miR-365a-3p、hsa-miR-574-3p、hsa-miR-29b-2-5p、hsa-miR-9-3p、hsa-miR-130b-3p、hsa-miR-331-3p、hsa-miR-454-3p、hsa-miR-15a-5p、hsa-miR-3613-5p、hsa-miR-628-5p、hsa-miR-5701、hsa-miR-335-5p、hsa-miR-4521、hsa-miR-590-3p、hsa-miR-548e-3p、hsa-miR-642a-5p、hsa-miR-1285-3p、hsa-miR-96-5p、hsa-miR-576-5p、hsa-miR-18a-5p、hsa-miR-17-3p、hsa-miR-659-5p、hsa-miR-3687、hsa-miR-514a-3p、hsa-miR-135a-5p、hsa-miR-144-5p、hsa-miR-324-3p、hsa-miR-190b、hsa-miR-1307-5p、hsa-miR-30d-3p、hsa-miR-6516-3p、hsa-miR-3607-3p、hsa-let-7f-1-3p、hsa-miR-7-1-3p、hsa-miR-26a-2-3p、hsa-miR-532-3p、hsa-miR-766-3p、hsa-miR-374b-3p、hsa-miR-324-5p、hsa-miR-4286、hsa-miR-26b-3p、hsa-miR-5100、hsa-miR-5096、hsa-miR-138-5p、hsa-miR-3940-3p、hsa-miR-3074-5p、hsa-miR-3913-5p、hsa-miR-450a-5p、hsa-miR-4491、hsa-miR-6516-5p、hsa-miR-24-1-5p、hsa-miR-1278、hsa-miR-1277-5p、hsa-miR-32-3p、hsa-miR-6087、hsa-let-7b-3p、hsa-miR-181c-5p、hsa-miR-548k、hsa-miR-6501-5p、hsa-miR-4791、hsa-miR-152-5p、hsa-miR-3912-3p、hsa-miR-4473、hsa-miR-33a-5p、hsa-miR-3928-3p、hsa-miR-93-3p、hsa-miR-3609、hsa-miR-1271-5p、hsa-miR-424-5p、hsa-miR-1277-3p、hsa-miR-4449、hsa-let-7g-3p、hsa-miR-3140-3p、hsa-miR-147b、hsa-miR-2355-3p、hsa-miR-5010-3p、hsa-miR-181c-3p、hsa-miR-6724-5p、hsa-miR-551b-5p、hsa-miR-2277-5p、hsa-miR-4999-5p、hsa-miR-3133、hsa-miR-5001-3p、hsa-miR-582-5p、hsa-miR-548q、hsa-miR-301a-5p、hsa-miR-3909、hsa-let-7c-3p、hsa-miR-504-5p、hsa-miR-326、hsa-miR-513c-5p、hsa-miR-4461、hsa-miR-494-3p、hsa-miR-4792、hsa-miR-548u、hsa-miR-548j-5p、hsa-miR-629-3p、hsa-miR-4746-5p、hsa-miR-3064-5p、hsa-miR-16-1-3p、hsa-miR-29a-5p、hsa-miR-6866-5p、hsa-miR-769-3p、hsa-miR-664b-3p、hsa-miR-7704、hsa-miR-5585-3p、hsa-miR-4742-3p、hsa-miR-6733-5p、hsa-miR-580-3p、hsa-miR-181b-3p、hsa-miR-1269b、hsa-miR-7977、hsa-miR-1249、hsa-miR-548b-5p、hsa-miR-130a-3p、hsa-miR-616-5p、hsa-miR-1304-5p、hsa-miR-509-3-5p、hsa-miR-4661-5p、hsa-miR-551b-3p、hsa-miR-491-5p、hsa-miR-1285-5p、hsa-miR-449c-5p、hsa-miR-1254、hsa-miR-20a-3p、hsa-miR-548am-3p、hsa-miR-5696、hsa-miR-660-3p、hsa-miR-4477b、hsa-miR-1306-5p、hsa-miR-548a-3p、hsa-miR-3651、hsa-miR-129-1-3p、hsa-miR-301b、hsa-miR-3614-3p、hsa-miR-4474-3p、hsa-miR-548ab、hsa-miR-616-3p、hsa-miR-98-3p、hsa-miR-222-5p、hsa-miR-33a-3p、hsa-miR-3179、hsa-miR-4781-3p、hsa-miR-873-5p、hsa-miR-6503-3p、hsa-miR-548n、hsa-miR-577、hsa-miR-5000-3p、hsa-miR-1269a、hsa-miR-369-3p、hsa-miR-34c-5p、hsa-miR-6511b-3p、hsa-miR-4787-3p、hsa-miR-506-3p、hsa-miR-627-3p、hsa-miR-4454、hsa-miR-643、hsa-miR-212-5p、hsa-miR-99a-3p、hsa-miR-548i、hsa-miR-1273c、hsa-miR-1343-3p、hsa-miR-4665-5p、hsa-miR-939-5p、hsa-miR-500a-5p、hsa-miR-6511a-3p、hsa-miR-548ay-5p、hsa-miR-501-5p、hsa-miR-7976、hsa-miR-627-5p、hsa-miR-382-3p、hsa-miR-7974，表达下调的hsa-miR-184、hsa-miR-197-5p、hsa-miR-6805-5p、hsa-miR-8072、hsa-miR-6851-5p、hsa-miR-10b-5p、hsa-miR-3154、hsa-miR-4745-5p、hsa-miR-4525、hsa-miR-122-5p、hsa-miR-6793-5p、hsa-miR-5090、hsa-miR-342-5p、hsa-miR-6780a-5p、hsa-let-7b-5p、hsa-miR-3198、hsa-miR-6825-5p、hsa-miR-6779-5p、hsa-miR-4755-5p、hsa-miR-760、hsa-miR-6734-5p、hsa-miR-92b-5p、hsa-miR-4467、hsa-miR-3191-3p、hsa-miR-193b-5p、hsa-miR-877-5p、hsa-miR-4459、hsa-miR-365b-5p、hsa-miR-3138、hsa-miR-6763-5p、hsa-miR-143-3p、hsa-miR-6741-5p、hsa-miR-4516、hsa-miR-214-3p、hsa-miR-1268b、hsa-miR-4647、hsa-miR-4498、hsa-miR-6853-3p、hsa-miR-200b-5p、hsa-miR-206、hsa-miR-5010-5p、hsa-miR-4446-3p、hsa-miR-145-3p、hsa-miR-6721-5p、hsa-miR-5187-5p、hsa-miR-6884-5p、hsa-miR-4436a、hsa-miR-7641、hsa-miR-1290、hsa-miR-3656、hsa-miR-4716-3p、hsa-miR-1538、hsa-miR-4734、hsa-miR-423-5p、hsa-miR-941、hsa-miR-3187-3p、hsa-miR-200a-5p、hsa-miR-203a、hsa-miR-3127-5p、hsa-miR-10a-5p、hsa-miR-664b-5p、hsa-miR-365a-5p、hsa-miR-6859-5p、hsa-miR-4687-3p、hsa-miR-4437、hsa-miR-1268a、hsa-miR-200b-3p、hsa-miR-6855-5p、hsa-miR-6515-5p、hsa-miR-3934-5p、hsa-miR-1246、hsa-miR-146b-3p、hsa-miR-296-3p、hsa-miR-320d、hsa-miR-486-5p、hsa-miR-4433b-3p、hsa-let-7e-5p、hsa-miR-1307-3p、hsa-miR-1306-3p、hsa-miR-2110、hsa-miR-4448、hsa-miR-320c、hsa-miR-320b。


2.一种与人类多发性骨髓瘤相关的miRNA表达图谱模型，其特征在于：与健康对照组相比，多发性骨髓瘤患者血清差异表达miRNAs包括表达上调的hsa-miR-30d-5p、hsa-miR-625-3p、hsa-miR-486-3p、hsa-miR-320b、hsa-miR-92b-3p、hsa-miR-22-3p、hsa-miR-320a、hsa-miR-375、hsa-miR-184、hsa-miR-197-3p、hsa-miR-7706、hsa-miR-4...

【专利技术属性】
技术研发人员：郝牧，魏晓晶，邱录贵，
申请(专利权)人：中国医学科学院血液病医院中国医学科学院血液学研究所，
类型：发明
国别省市：天津;12