lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway.
lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway.
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lncRNA CASC19 通过 AMPK-mTOR 途径促进自噬，从而促进鼻咽癌的放射抗性
DOI：
10.3390/ijms22031407
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发表时间：
2021-01-30
影响因子：
5.6
通讯作者：
Shao C
中科院分区：
文献类型：
--
作者：
Liu H;Zheng W;Chen Q;Zhou Y;Pan Y;Zhang J;Bai Y;Shao C
鼻咽癌（Nasopharyngeal carcinoma，NPC）是头颈部最常见的恶性肿瘤之一，主要采用放射治疗。然而，放射抵抗仍然是成功治疗NPC的严重障碍。本研究的目的是揭示鼻咽癌放射抵抗的机制，并阐明在鼻咽癌放射敏感性调节中可能起重要作用的新基因。通过对鼻咽癌细胞系CNE 2及其辐射抗性细胞系CNE 2 R的RNA-seq分析，筛选出lncRNA CASC 19作为候选的辐射抗性标记。体内外实验结果表明，鼻咽癌细胞中CASC 19的高表达与鼻咽癌的放射抵抗性呈正相关，CASC 19的敲低可显著提高鼻咽癌细胞的放射敏感性。与CNE 2和另一种NPC细胞系HONE 1相比，CNE 2 R中自噬的发生率增加，并且用LC 3 siRNA（siLC 3）沉默自噬使NPC细胞对辐射敏感。此外，CASC 19 siRNA（siCASC 19）通过抑制AMPK/mTOR通路抑制细胞自噬，并通过PARP 1通路促进细胞凋亡。我们的研究结果首次揭示了lncRNA CASC 19通过调节自噬而促进鼻咽癌的放射抗性。CASC 19可能成为鼻咽癌潜在的分子生物学标志物和新的治疗靶点。
Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.
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