Chuerduangphui Jureeporn, Ekalaksananan Tipaya, Chaiyarit Ponlatham, Patarapadungkit Natcha, Chotiyano Apinya, Kongyingyoes Bunkerd, Promthet Supannee, Pientong Chamsai
Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
PLoS One. 2018 Jan 31;13(1):e0192009. doi: 10.1371/journal.pone.0192009. eCollection 2018.
Arecoline, the major alkaloid of areca nut, is known to induce oral carcinogenesis, however, its mechanism is still needed to elucidate. This study investigated the effects of arecoline on cell viability and cell-cycle progression of oral squamous cell carcinoma (OSCC) cells as well as a relevant cellular gene expression. The results showed that a low concentration of arecoline (0.025 μg/ml) increased OSCC cell viability, proportion of cells in G2/M phase and cell proliferation. Simultaneously, it induced IL-6, STAT3 and c-Myc expression. Interestingly, c-myc promoter activity was also induced by arecoline. MiR-22 expression in arecoline-treated OSCC cells was suppressed and comparable to an upregulated c-Myc expression. In arecoline-treated OSCC cells, oncostatin M (OSM) expression was significantly upregulated and inversely correlated with miR-22 expression. Likewise, OSM expression and its post-transcriptional activity were significantly decreased in miR-22-transfected OSCC and 293FT cells. This result demonstrated that miR-22 directly targeted OSM. Interestingly, miR-22 played an important role as a tumor suppresser on suppressing cell proliferation, migration and cell-cycle progression of OSCC cells. This result suggested the effect of arecoline to promote cell proliferation and cell-cycle progression of OSCC cells might be involved in induction of c-Myc expression and reduction of miR-22 resulting in OSM upregulation.
槟榔碱是槟榔的主要生物碱，已知其可诱发口腔癌，但仍需阐明其机制。本研究调查了槟榔碱对口腔鳞状细胞癌（OSCC）细胞活力、细胞周期进程以及相关细胞基因表达的影响。结果表明，低浓度槟榔碱（0.025μg/ml）可提高OSCC细胞活力、G2/M期细胞比例及细胞增殖能力。同时，它还诱导白细胞介素-6（IL-6）、信号转导和转录激活因子3（STAT3）及c-Myc的表达。有趣的是，槟榔碱还可诱导c-myc启动子活性。槟榔碱处理的OSCC细胞中miR-22的表达受到抑制，且与上调的c-Myc表达相当。在槟榔碱处理的OSCC细胞中，制瘤素M（OSM）表达显著上调，且与miR-22表达呈负相关。同样，在转染miR-22的OSCC和293FT细胞中，OSM表达及其转录后活性显著降低。这一结果表明miR-22直接靶向OSM。有趣的是，miR-22作为一种肿瘤抑制因子，在抑制OSCC细胞增殖、迁移和细胞周期进程中发挥着重要作用。这一结果表明，槟榔碱促进OSCC细胞增殖和细胞周期进程的作用可能与诱导c-Myc表达及降低miR-22从而导致OSM上调有关。
