Cui Pengfei, Xin Deqian, Li Fu, Deng Lin, Gao Yujie
Department of Anesthesiology, Yantaishan Hospital, Yantai, China.
Department of Anesthesiology, YanTai Yuhuangding Hospital, Yantai, China.
Front Oncol. 2022 Feb 24;12:775132. doi: 10.3389/fonc.2022.775132. eCollection 2022.
Butorphanol, a partial agonist of opioid receptor κ 1 receptor, can and is widely used as an analgesic drug to relieve moderate and severe pain in clinic. Osteosarcoma is one of the most common malignant bone tumor in adolescents under the age of 20. To our knowledge no study has investigated the effect of butorphanol on the proliferation of osteosarcoma cells. In this study, The proliferation of osteosarcoma cells was measured by CCK-8 and colony formation assays, and the migration of osteosarcoma cells were detected by scratch and transwell assays. The expression of piRNA was detected by RNA sequencing and real-time PCR. PiRNA mimics or inhibitors have been used to upregulate or inhibit piRNA expression in osteosarcoma cells, respectively. We found that butorphanol, at the concentration of 10ug/ml or higher, could significantly inhibit the proliferation and migration of osteosarcoma cells. Our resuslts indicated that butorphanol promoted the expression of piRNA hsa_piR_006613 and overexpression of piRNA hsa_piR_006613 inhibited the proliferation and migration of osteosarcoma cells. our study also showed that inhibition of the expression of piRNA hsa_piR_006613 could promote the proliferation and migration of osteosarcoma cells. Butorphanol played the regulatory role on osteosarcoma cells in dependent of piRNA hsa_piR_006613. Butorphanol was found to inhibit the proliferation and migration of osteosarcoma cells by promoting piRNA hsa_piR_006613 expression. Bioinformatics analysis showed that hsa_piR_006613 downregulated FN1 protein expression by binding with 3'-UTR of FN1 mRNA. In all, the present research indicated that butorphanol suppresses the proliferation of osteosarcoma by promoting the expression of piRNA hsa_piR_006613, which downregulated the expression of FN1. Has_piR_006613 may become a new therapeutic target for osteosarcoma.
布托啡诺是阿片受体κ1受体的部分激动剂，能够且已在临床上广泛用作镇痛药来缓解中度和重度疼痛。骨肉瘤是20岁以下青少年中最常见的恶性骨肿瘤之一。据我们所知，尚无研究调查布托啡诺对骨肉瘤细胞增殖的影响。在本研究中，通过CCK-8和集落形成试验检测骨肉瘤细胞的增殖，通过划痕试验和Transwell试验检测骨肉瘤细胞的迁移。通过RNA测序和实时PCR检测piRNA的表达。分别使用piRNA模拟物或抑制剂上调或抑制骨肉瘤细胞中piRNA的表达。我们发现，浓度为10μg/ml及以上的布托啡诺可显著抑制骨肉瘤细胞的增殖和迁移。我们的结果表明，布托啡诺促进piRNA hsa_piR_006613的表达，而piRNA hsa_piR_006613的过表达抑制骨肉瘤细胞的增殖和迁移。我们的研究还表明，抑制piRNA hsa_piR_006613的表达可促进骨肉瘤细胞的增殖和迁移。布托啡诺通过piRNA hsa_piR_006613对骨肉瘤细胞发挥调节作用。发现布托啡诺通过促进piRNA hsa_piR_006613的表达来抑制骨肉瘤细胞的增殖和迁移。生物信息学分析表明，hsa_piR_006613通过与FN1 mRNA的3'-UTR结合而下调FN1蛋白的表达。总之，本研究表明布托啡诺通过促进piRNA hsa_piR_006613的表达来抑制骨肉瘤的增殖，而piRNA hsa_piR_006613下调了FN1的表达。Has_piR_006613可能成为骨肉瘤的一个新的治疗靶点。
