Cui Zheqing, Pu Tian, Zhang Yujie, Wang Jia, Zhao Yulin
Department of Rhinology, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan 450052, People's Republic of China.
Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan 450052, People's Republic of China.
Open Biol. 2020 May;10(5):190286. doi: 10.1098/rsob.190286. Epub 2020 May 13.
Cisplatin has been used as the first-line chemotherapy to treat advanced nasopharyngeal carcinoma (NPC), while acquired cisplatin resistance resulting from epigenetic regulation is not well understood. The relative expression of LINC00346 was detected in healthy persons, cisplatin-sensitive (CS) patients and cisplatin-resistant (CR) patients. The regulatory effect of LINC00346 on the proliferation was detected by cell-counting kit-8. Apoptosis was assayed by histone/DNA ELISA and Caspase-3 activity. Clonal formation and cisplatin resistance were also deciphered. Luciferase reporter and RNA immunoprecipitation assay were adopted to study the interaction between LINC00346 and miR-342-5p. LINC00346 was highly expressed in NPC patients, especially in CR patients, which was associated with cisplatin resistance and poor prognosis. Inhibition of LINC00346 expression promoted cisplatin sensitivity of NPC cells, while LINC00346 over-expression promoted cisplatin resistance of NPC cells. miR-342-5p expression was negatively correlated with cisplatin resistance, and microRNA-342-5p siRNAs treatment could rescue the cisplatin resistance diminished by LINC00346 inhibition. It was further found that miR-342-5p was negatively regulated by LINC00346. In conclusion, LINC00346 regulates the cisplatin resistance of NPC cells by inhibiting miR-342-5p, which could provide a potential target for chemotherapy resistance.
顺铂一直被用作治疗晚期鼻咽癌(NPC)的一线化疗药物,然而,由表观遗传调控导致的获得性顺铂耐药性尚未得到充分了解。检测了健康人、顺铂敏感(CS)患者和顺铂耐药(CR)患者中LINC00346的相对表达。通过细胞计数试剂盒-8检测LINC00346对增殖的调节作用。通过组蛋白/DNA ELISA和Caspase-3活性检测细胞凋亡。还分析了克隆形成和顺铂耐药性。采用荧光素酶报告基因和RNA免疫沉淀试验研究LINC00346与miR-342-5p之间的相互作用。LINC00346在NPC患者中高表达,尤其是在CR患者中,这与顺铂耐药性和预后不良相关。抑制LINC00346表达可提高NPC细胞对顺铂的敏感性,而LINC00346过表达则促进NPC细胞对顺铂的耐药性。miR-342-5p表达与顺铂耐药性呈负相关,miRNA-342-5p siRNAs处理可挽救因LINC00346抑制而减弱的顺铂耐药性。进一步发现,LINC00346对miR-342-5p起负调控作用。总之,LINC00346通过抑制miR-342-5p调节NPC细胞的顺铂耐药性,这可能为化疗耐药提供一个潜在靶点。