Epidemiology of nasopharyngeal carcinoma

Radioresistance is a major obstacle in successful clinical cancer radiotherapy, and the underlying mechanisms are not clear. Here we show that IKKα-mediated miR-196a biogenesis via interaction with Drosha regulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy. Phosphorylation of IKKα at T23 site (p-IKKαT23) promotes the binding of IKKα to Drosha that accelerates the processing of miR-196a primary transcripts, leading to increased expressions of both precursor and mature miR-196a. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment. The miR-196a mimic suppresses while its inhibitor promotes the resistance of NPC to radiation treatment. Importantly, the expression of p-IKKαT23 is positively related to the expression of miR-196a in human NPC tissues, and expression of p-IKKαT23 and miR-196a is inversely correlated with NPC clinical radioresistance. Thus, our studies establish a novel mechanistic link between the inactivation of IKKαT23-Drosha-miR-196a pathway and NPC radioresistance, and de-inactivation of IKKαT23-Drosha-miR-196a pathway would be an efficient way to restore the sensitivity of radioresistant NPC to radiotherapy.

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“…1 About 90% of NPC are undifferentiated carcinoma. Radiation therapy is the primary treatment for undifferentiated NPC.…”

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confidence: 99%

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

et al. 2016

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“…Nasopharyngeal cancer (NPC) is a neoplasm of the head and neck that is prevalent in South‐East Asia 1, 2, 3. Although the radiotherapy can control early stage of NPC, tumor recurrence and distant metastasis are the key difficulties of NPC therapy 4, 5, 6, 7.…”

Section: Introductionmentioning

confidence: 99%

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

Lin

Ding

et al. 2018

Cancer Medicine

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Rho GTPase‐activating protein 42 was identified as an inhibitor of RhoA to maintain normal blood pressure homeostasis. However, the effect of ARHGAP42 in promoting cell malignancy in nasopharyngeal carcinoma is demonstrated in this study. Microarray and real‐time quantitative PCR were used for a mRNA profiling of ARHGAP42 in nasopharyngeal primary and metastatic carcinoma tissues. Western blot and immunohistochemical staining were used for detecting the expression of ARHGAP42 protein in nasopharyngeal carcinoma tissues and cell lines. The overexpression and silence experiments of ARHGAP42 were performed in NPC cell lines using siRNA and expressive plasmid for evaluating cancer cell migration and invasion in vitro. Real‐time quantitative PCR, western blot, and transwell test were employed for with the function of ARHGAP42 and its antisense lncRNA uc010rul. We confirmed the elevated expression of ARHGAP42 in metastatic NPC tissues of mRNA and protein for the first time. Immunohistochemical analysis indicated that NPC patients with highly ARHGAP42 expression were significantly associated with shorter metastasis‐free survival. Knockdown of ARHGAP42 resulted in significant inhibition of nasopharyngeal cancer cell migration and invasion in vitro, and the overexpression of ARHGAP42 showed the opposite effects. In addition, the silence of uc010rul resulted in ARHGAP42 expression decrease and significant inhibition of nasopharyngeal cancer cell migration and invasion. High expression of ARHGAP42 is associated with poor metastasis‐free survival of nasopharyngeal carcinoma patients. ARHGAP42 promotes migration and invasion of nasopharyngeal carcinoma cells in vitro; the antisense lncRNA may be involved in this effect.

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“…Nasopharyngeal carcinoma (NPC), a rare disease in Western countries, occurs with a high frequency in southern China and Southeast Asia, Northern Africa, and Alaska [1]. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of most NPCs [2].…”

Section: Introductionmentioning

confidence: 99%

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein–Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines

Chang

Chiosea

Altman

et al. 2016

Head and Neck Pathol

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Most nasopharyngeal carcinomas (NPCs) in a high-incidence population are driven by Epstein-Barr virus (EBV) infection. EBV-associated malignancies have increased expression of the programmed death-ligand 1 (PD-L1). Immunotherapy agents targeting the PD-1/PD-L1 pathway have achieved durable treatment effects in patients with various cancer types including EBV-associated malignancies. In this study, we sought to investigate PD-L1 expression in a cohort of patients with NPCs from the Philippines. Fifty-six NPCs were studied for PD-L1, p16, and DNA mismatch repair (MMR) deficiency by immunohistochemistry. One case with MMR deficiency was also assessed for microsatellite instability (MSI) by polymerase chain reaction. EBV and human papillomavirus (HPV) status were tested by in situ hybridization. All NPCs were p16 negative. Three of the 56 NPCs (5%) were EBV negative (EBV-) and HPV negative, while one NPC (1/56, 2%) was EBV positive and showed MSI (EBV?/MSI). Positive PD-L1 expression (PD-L1?), defined as membranous staining in C1% tumor cells, was seen in 64% (36/56) of NPCs. All three EBV-NPCs were PD-L1? as was the EBV?/MSI NPC. PD-L1? was seen significantly more often in NPCs from non-smokers than those from smokers (23/28, 82% vs 9/18, 50%; P = 0.047). PD-L1? was not associated with pT, pN, distant metastasis, or clinical stage (P [ 0.05). PD-L1? was not associated with overall survival (P = 0.473). In summary, our results show frequent PD-L1 expression in NPCs regardless of EBV status and a preferential PD-L1 expression in non-smokers. MSI and HPV positivity are exceedingly rare in NPCs.

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Epidemiology of nasopharyngeal carcinoma

Cited by 775 publications

References 38 publications

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein–Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines

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