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RIG-I promotes IFN/JAK2 expression and the endoplasmic reticulum stress response to inhibit chemoradiation resistance in nasopharyngeal carcinoma.

ABSTRACT: RIG-I is associated with the occurrence and development of many tumors. However, the role of RIG-I in radiotherapy and chemotherapy in NPC has not been reported to date. In our study, RIG-I expression was significantly reduced in chemoradiotherapy-resistant NPC tissues and cells compared with that in therapy-sensitive tissues and cells. RIG-I expression increased in nonresistant NPC cells, including CNE1 and CNE2, in a dose-dependent manner with increasing chemotherapy drug concentration or radiotherapy dose. RIG-I overexpression promoted radiotherapy and chemotherapy sensitivity in NPC cells, leading to cellular apoptosis and increased expression of the proapoptotic factors BAX and caspase-3. Similarly, RIG-I knockdown in NPC cells promoted chemoradiotherapy resistance and reduced apoptosis. Analysis of microarray data indicated that the expression of IFN/JAK2 and endoplasmic reticulum (ER) stress response markers, such as JAK2, STAT1, IRF9, IFNB1, IRF3, p-IRF3, XBP1, ATF6, IFIT2, and ISG15, was inhibited in chemoradiotherapy-resistant cells compared with that in sensitive cells. Conversely, activation of IFN/JAK2 and ER stress response pathways in NPC cells reduced paclitaxel resistance and increased apoptosis. RIG-I promotes IFN/JAK2 and ER stress response-mediated apoptosis to inhibit chemoradiation resistance in nasopharyngeal carcinoma.

SUBMITTER: Jing D

PROVIDER: S-EPMC6797570 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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RIG-I promotes IFN/JAK2 expression and the endoplasmic reticulum stress response to inhibit chemoradiation resistance in nasopharyngeal carcinoma.

Jing Di D Zhou Weibing W Shen Lin L Zhang Qian Q Xie Wang-Ti WT Shen Erdong E Li Zhi Z Shen Liang-Fang LF Sun Lun-Quan LQ

Cancer medicine 20190828 14

RIG-I is associated with the occurrence and development of many tumors. However, the role of RIG-I in radiotherapy and chemotherapy in NPC has not been reported to date. In our study, RIG-I expression was significantly reduced in chemoradiotherapy-resistant NPC tissues and cells compared with that in therapy-sensitive tissues and cells. RIG-I expression increased in nonresistant NPC cells, including CNE1 and CNE2, in a dose-dependent manner with increasing chemotherapy drug concentration or radi ...[more]

PMID: 31464090

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Project description:There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system. The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO. And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC). The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test, univariate and multivariate logistic regression analyses. We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients. CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy. And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression. In conclusion, SNPs of VCP rs2074549, CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.

Dataset Information

RIG-I promotes IFN/JAK2 expression and the endoplasmic reticulum stress response to inhibit chemoradiation resistance in nasopharyngeal carcinoma.

Publications

RIG-I promotes IFN/JAK2 expression and the endoplasmic reticulum stress response to inhibit chemoradiation resistance in nasopharyngeal carcinoma.

Similar Datasets

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