Yiwen You

Long non-coding RNA ROR promotes proliferation, migration and chemoresistance of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies of the head and neck. It arises from the nasopharynx epithelium and is associated with high morbidity and mortality. Long non‐coding RNA (lncRNA) have been reported to regulate gene interaction and play critical roles in carcinogenesis and progression. LncRNA‐ROR, a recently identified lncRNA, has been shown to be involved in initiation, progression and metastasis of several tumors, including hepatocellular carcinoma, breast cancer and glioma. However, whether lncRNA‐ROR is associated with the progression of NPC remains unknown. Resistance to radiotherapy and chemotherapy is the primary cause of NPC patients’ death. In this study, we found that lncRNA‐ROR was significantly upregulated in NPC tissues compared with normal tissues. Next, our study proved that lncRNA‐ROR was highly associated with the proliferation, metastasis and apoptosis of NPC. The enrichment of lncRNA‐ROR played a critucal functional role in chemoresistance. The mechanism by which NPC resists chemotherapy might be that lncRNA‐ROR suppress p53 signal pathway. Taken together, these data suggested that lncRNA‐ROR played an important role in the progression of NPC; thereby it might become a therapeutic target and reduce chemoresistance for NPC.

Matrix metalloproteinase 13-containing exosomes promote nasopharyngeal carcinoma metastasis.

Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13‐containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients’ plasma. Transwell analysis revealed that MMP13‐containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13‐containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13‐containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.

Effects of ADAM10 upregulation on progression, migration, and prognosis of nasopharyngeal carcinoma

A disintegrin and metalloprotease 10 (ADAM10) is a typical member of the ADAMs family, which has been reported to be upregulated in various types of cancers and contribute to cancer progression and metastasis. However, little is known about the role of ADAM10 in nasopharyngeal carcinoma (NPC). The purpose of this study is to explore ADAM10 expression status and its biological functions in NPC. We first examined the expression of ADAM10 in NPC tissues and cell lines by immunohistochemistry, Western blotting, PCR, and immunofluorescence analysis. We observed that ADAM10 was significantly elevated in NPC and its expression level was correlated with T classification (P = 0.044), distant metastasis (P = 0.016), TNM clinical stage (P = 0.013), and proliferation marker Ki‐67 expression (P = 0.001). Patients with NPC with high expression of ADAM10 had shorter overall survival rates. In addition, knockdown of ADAM10 by RNAi was found to inhibit the CNE‐2 cell proliferation and migration. Our findings hinted that overexpression of ADAM10 promotes the progression and migration of NPC, which makes it a potential therapeutic target for the treatment of tumor metastases in NPC.

Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma

HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment.

MicroRNA-338 inhibits migration and proliferation by targeting hypoxia-induced factor 1α in nasopharyngeal carcinoma

Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. An increasing number of studies have shown that microRNAs (miRNAs) play a key role in the development and progression of NPC. miR-338-3p has been demonstrated as an anti-oncogene in different solid tumors. The aim of the present study was to investigate the potential role of miR‑338-3p in the development and progression of NPC. Compared with normal samples, our data showed that miR-338-3p were downregulated in NPC tissues and cells. The luciferase assay demonstrated that HIF-1α was a direct target of miR-338-3p. We also found that miR-338-3p regulated the expression levels of HIF-1α, respectively. Overexpression of miR-338-3p in NPC cells significantly inhibited cell proliferation, and migration. Conversely, miR-338-3p knockdown in cells with lower endogenous expression levels significantly reduced antitumor behavior. Furthermore, enforced expression of miR-338-3p led to a decline in ERK phosphorylation as well as inhibited the hypoxia induced epithelial to mesenchymal transition. Cells pre-transfected with miR-338-3p can overcome hypoxia-mediated cisplatin resistance. Taken together, we found that miR-338-3p directly targeted HIF-1α, and we provide insight into NPC initiation and progression, possibly representing a novel therapeutic target.

Clinical significance of HAX-1 expression in laryngeal carcinoma.

OBJECTIVE HS1-associated protein X-1 (HAX-1) is a multifunctional protein that has been highlighted as an important marker in many types of cancers. However, little is known about the role of HAX-1 in laryngeal carcinoma. The purpose of the present study is to explore HAX-1 expression status and its associations with clinicopathologic features and survival in a well-defined cohort of laryngeal carcinoma. METHODS We examined the expression of HAX-1 at protein and mRNA levels in laryngeal carcinoma tissues and adjacent non-tumor tissues by immunohistochemistry, Western blotting and two-step quantitative real-time PCR analysis, respectively. RESULTS We observed that HAX-1 was significantly elevated in laryngeal carcinoma. The relationship between the levels of HAX-1 expression and clinicopathologic characteristics was then analyzed. Overexpression of HAX-1 was significantly correlated with T classification, lymph node metastasis, clinical stage, and pathology. Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. We find that patients with overexpression of HAX-1 had shorter overall survival rates. Finally, the significance of various survival variables was analyzed using multivariate Cox proportional hazards model. We found that overexpression of HAX-1 was an independent prognostic factor for patients with laryngeal carcinoma. CONCLUSION Our findings hinted that overexpression of HAX-1 was a potentially unfavorable factor in the progression and prognosis of laryngeal carcinoma.

Aberrant Kif2a and Ki67 expression predicts poor survival in laryngeal squamous cell carcinoma

OBJECTIVE Previous studies have demonstrated that aberrant Kif2a expression is associated with tumor aggressiveness and poor prognosis in various human cancers. However, the clinicopathological significance of Kif2a in laryngeal squamous cell carcinoma (LSCC) is unknown. The aim of this study is to analyze the prognostic significance of Kif2a, alone and in combination with Ki67 protein expression, in LSCC patients. METHODS We examined the expression status of Kif2a and Ki67 protein in 165 laryngeal tissues (137 primary tumors and 28 cases of matched normal surgical margins) by immunohistochemistry (IHC) analysis using tissue microarrays. RESULTS We found that expression correlated with clinical parameters and overall survival (OS). Our results revealed that Kif2a and Ki67 protein expression was significantly higher in cancerous tissues compared to normal surgical margins. High Kif2a protein expression (Kif2a+) was significantly associated with tumor stage (P=0.026) and cervical lymph node metastasis (P=0.034). A significant correlation between Kif2a and Ki67 protein expression was observed (P=0.040). Multivariate analysis revealed that patients with Kif2a+ (hazard ratio [HR] 3.640, 95% confidence interval [CI] 1.253-10.570; P=0.018) and high Ki67 (Ki67+) expression (HR 3.086, 95%CI 1.016-9.371; P=0.047) had poor OS. CONCLUSION We speculate that Kif2a and Ki67 can be used as prognostic markers for LSCC patients.

Foxj2 overexpression is associated with poor prognosis, progression, and metastasis in nasopharyngeal carcinoma

Foxj2, a novel member of Forkhead box family, has been reported to play an important role in tumorigenesis, progression, and metastasis of certain cancers. However, the expression status and effects of Foxj2 on nasopharyngeal carcinoma (NPC) progression and metastasis remain debated. In this study, we first examined the expression of Foxj2 in NPC by immunohistochemistry and Western blotting analysis. We confirmed significantly elevated expression of Foxj2 in NPC tissues and cell lines. Next, the relationships between Foxj2 expression levels and the clinicopathological factors were investigated. Its expression level correlated with T-classification (P=0.026), distant metastasis (P=0.004), and clinical stage (P=0.029). In addition, high expression of Foxj2 was associated with poor prognosis in NPC patients. The effects of Foxj2 on cell proliferation and migration were explored by RNA interference (RNAi) with CCK-8 assay, cell cycle analyses, wound healing, and transwell assay. In conclusion, our data indicate that Foxj2 upregulation promotes the progression and migration of NPC. It makes Foxj2 serve as a potential therapeutic target for the treatment of NPC.

PFKFB3 promotes proliferation, migration and angiogenesis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a squamous epithelial cancer, arising from the nasopharynx epithelium. It has high morbidity and mortality. PFKFB3 as a glycolytic activator has been implicated in the progression of multiple types of tumor. PFKFB3 can be contributed to the progression and metastasis of cancer. However, whether PFKFB3 is associated with the progression of NPC remains unknown. We postulated that PFKFB3 promotes proliferation, migration and angiogenesis in nasopharyngeal carcinoma. In this study, we found that PFKFB3 was significantly up-regulated in NPC tissues and cell lines compared with normal control. Our study proved that PFKFB3 can regulate the proliferation, metastasis and apoptosis of NPC. By the way, the NPC-derived exosomes come from and CNE2-derived exosomes are enriched in PFKFB3. The enrichment of PFKFB3 played a crucial functional role in promotes HUVECs proliferation, migration and angiogenesis. And tumor angiogenesis is closely related to the proliferation and metastasis of tumor. In conclusion, our findings demonstrate that PFKFB3 could act not only as a clinical biomarker for angiogenesis but also as a therapeutic target to overcome angiogenesis, enhancing the clinical benefits of angiogenesis therapy in NPC patients.

High Gpx1 expression predicts poor survival in laryngeal squamous cell carcinoma

OBJECTIVE Several studies have demonstrated that abnormal glutathione peroxidases 1 (Gpx1) expression can influence the biological behavior of malignant cells. However, the roles of Gpx1 in laryngeal squamous cell carcinoma (LSCC) remain unknown. The purpose of this study is to analyze the Gpx1 expression and prognostic significance in LSCC patients. METHODS Gpx1 mRNA levels in laryngeal tissues were determined by qRT-PCR. Meanwhile, We examined the expression levels of Gpx1 protein in 140 primary tumor tissues and 28 cases of normal tissues by immunohistochemistry (IHC) analysis on tissue microarrays (TMA). RESULTS Our results revealed that the frequency of high Gpx1 was significantly higher in cancer tissue compared to normal surgical margins; Gpx1 expression correlated with clinical features and overall survival (OS). Gpx1 overexpression was significantly associated with lymph node metastasis (P=0.023) and TNM stage (P=0.008); Kaplan-Meier survival curves revealed that patients with high Gpx1 expression had worse prognoses than patients with low Gpx1 expression; By multivariate analysis, we revealed that high Gpx1 expression level (HR 2.101, 95%CI 1.011-4.367; P=0.047) was an independent prognostic factor of survival in LSCC patients. CONCLUSION We speculate that Gpx1 can be applied to predict the prognosis in LSCC patients.