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.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies,[1] with a high incidence in Southern China and Southeast Asia.[2]
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
The results indicated that Bax and caspase‐3 expression was significantly increased in Retinoic acid‐inducible gene I (RIG‐I)‐overexpressing cells after radiation (Figure 2C,D)
Summary
Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies,[1] with a high incidence in Southern China and Southeast Asia.[2]. Previous studies reported that viral RNA can bind to the RIG‐I receptor, thereby activating the RIG‐I signaling pathway, as well as inflammatory and IRF3 signaling pathways, to induce IFN signaling and block viral invasion.[17,18,19] Recent studies on RIG‐I in cancer have revealed that high RIG‐I expression is associated with lower survival rates in patients with pancreatic ductal carcinoma and that RIG‐I promotes cancer cell growth. We used radiotherapy‐ and chemotherapy‐resistant NPC cell lines to investigate how RIG‐I regulates chemoradiation resistance and to identify the underlying mechanisms. We found that RIG‐I regulates IFN/JAK2 and (ER) stress response‐mediated apoptosis to affect paclitaxel resistance in NPC. We propose that this mechanism may be a new target for combination drug therapy in NPC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
