Liu Xingguang, Zhao Tengda, Yuan Zhe, Ge Shaohua
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, 250012, China.
Department of Oral and Maxillofacial surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Cell Death Discov. 2022 Apr 20;8(1):216. doi: 10.1038/s41420-022-01000-w.
There is increasing evidence that dysregulated long non-coding RNA (lncRNA) is implicated in tumorigenesis and progression. We aim to explore the role of lncRNA MIR600HG in glycometabolism and cisplatin (DDP) resistance of oral squamous cell carcinoma (OSCC) cells via regulating microRNA-125a-5p (miR-125a-5p) and RING finger 44 (RNF44). Expression of MIR600HG, miR-125a-5p, and RNF44 in OSCC clinical samples, cell lines, and DDP-resistant OSCC cells (SCC-9/DDP) was determined. In SCC-9 cells, proliferation, IC value of DDP, migration, invasion, and apoptosis were detected; in SCC-9/DDP cells, proliferation, IC value of DDP, apoptosis, glucose consumption, and production of lactic acid and ATP were evaluated. The interaction of MR600HG, miR-125a-5p, and RNF44 was verified. MIR600HG and RNF44 were upregulated while miR-125a-5p was downregulated in OSCC tissues and cell lines, and also in SCC-9/DDP cells. In SCC-9 cells, MIR600HG overexpression improved cell growth, metastasis, and inhibited cell susceptibility to DDP; in SCC-9/DDP cells, silencing of MIR600HG promoted apoptosis, improved DDP sensitivity, and inhibited cell glycolysis. Downregulation of miR-125a-5p showed the opposite effect to downregulation of MIR600HG. MIR600HG bound to miR-125a-5p and miR-125a-5p targeted RNF44. Downregulation of miR-125a-5p reversed the improvement of DDP sensitivity and the inhibition of cell glycolysis by downregulated MIR600HG on SCC-9/DDP cells. Downregulating RNF44 reversed the promotion of DDP resistance and cell glycolysis of SCC-9/DDP cells mediated by downregulation of miR-125a-5p. Collectively, our study addresses that MIR600HG downregulation elevates miR-125a-5p and reduces RNF44 expression, thereby improving DDP sensitivity and inhibiting glycolysis in DDP-resistant OSCC cells.
越来越多的证据表明，长链非编码RNA（lncRNA）失调与肿瘤发生和进展有关。我们旨在通过调节微小RNA-125a-5p（miR-125a-5p）和环指蛋白44（RNF44）来探讨lncRNA MIR600HG在口腔鳞状细胞癌（OSCC）细胞糖代谢和顺铂（DDP）耐药中的作用。测定了MIR600HG、miR-125a-5p和RNF44在OSCC临床样本、细胞系及耐DDP的OSCC细胞（SCC-9/DDP）中的表达。在SCC-9细胞中，检测其增殖、DDP的半数抑制浓度（IC值）、迁移、侵袭及凋亡情况；在SCC-9/DDP细胞中，评估其增殖、DDP的IC值、凋亡、葡萄糖消耗以及乳酸和三磷酸腺苷（ATP）的产生。验证了MR600HG、miR-125a-5p和RNF44之间的相互作用。在OSCC组织、细胞系以及SCC-9/DDP细胞中，MIR600HG和RNF44上调，而miR-125a-5p下调。在SCC-9细胞中，MIR600HG过表达促进细胞生长、转移，并降低细胞对DDP的敏感性；在SCC-9/DDP细胞中，沉默MIR600HG可促进凋亡、提高DDP敏感性并抑制细胞糖酵解。miR-125a-5p下调产生的效应与MIR600HG下调相反。MIR600HG与miR-125a-5p结合，且miR-125a-靶向RNF44。miR-125a-5p下调可逆转MIR600HG下调对SCC-9/DDP细胞DDP敏感性的改善及对细胞糖酵解的抑制。下调RNF44可逆转miR-125a-5p下调介导的SCC-9/DDP细胞对DDP的耐药性及细胞糖酵解的促进作用。总的来说，我们的研究表明，MIR600HG下调可提高miR-125a-5p水平并降低RNF44表达，从而提高耐DDP的OSCC细胞对DDP的敏感性并抑制糖酵解。
