SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma

Li, Yang; Lv, Yumin; Chen, Cheng; Huang, Yan; Liu, Yang; He, Jingjing; Tao, Xingyu; Hu, Yingying; Ma, Yuting; Su, Yun; Wu, Liyang; Yu, Guangrong; Jiang, Qingping; Liu, Shu; Liu, Xiong; Liu, Zhen

doi:10.1038/s41419-020-2699-2

Cited by 23 publications

(23 citation statements)

References 37 publications

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“…Finally, the current study sought to define the underlying mechanism of the effect of gal-3 on NPC cells. The activation of the ERK1/2 and Akt signaling pathways is involved in the proliferation, migration, invasion, metastasis and radiosensitivity of NPC (38)(39)(40). However, whether gal-3 affects the ERK1/2 and Akt signaling pathways of NPC cell lines remains unknown.…”

Section: Expression Levels Of Gal-3 ---------------------------------mentioning

confidence: 99%

Galectin‑3 facilitates the proliferation and migration of nasopharyngeal carcinoma cells via activation of the ERK1/2 and Akt signaling pathways, and is positively correlated with the inflammatory state of nasopharyngeal carcinoma

Chen

Liu

et al. 2021

Mol Med Rep

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Nasopharyngeal carcinoma (NPC) is an epithelial carcinoma originating from the nasopharyngeal mucosal tissue and is highly prevalent in southeast Asia. Galectin-3 (gal-3) serves crucial roles in many cancers but its role in NPC remains to be elucidated. The aim of the present study was to investigate the role of gal-3 in NPC. Immunohistochemistry and ELISA were used to determine the expression level of gal-3 in patients with NPC or chronic rhinitis (CR). Gal-3 short hairpin (sh)RNA was established to knockdown gal-3 in 5-8F and 6-10B cells, allowing for the evaluation of the roles of gal-3 in proliferation, migration and apoptosis in NPC cell lines. Immunohistochemistry staining of IL-6 and IL-8 was applied to access the inflammatory state of tumor tissues, and the correlation between the inflammatory state and gal-3 was analyzed. The results demonstrated that gal-3 was upregulated in patients with NPC compared with patients with CR. Knockdown of gal-3 inhibited proliferation and migration in 5-8F and 6-10B cells, as well as promoted apoptosis in these cells. The expression levels of MMP-9 and IL-8 were also decreased in 5-8F and 6-10B cells after transfection with gal-3 shRNA. A positive correlation was identified between the expression level of gal-3 and the inflammatory state of NPC. The phosphorylation levels of ERK1/2 and Akt were downregulated after knockdown of gal-3 in 5-8F and 6-10B cells. In conclusion, the expression level of gal-3 was upregulated in patients with NPC and was positively correlated with the inflammatory state of NPC. The results suggested that gal-3 promoted the proliferation and migration of 5-8F and 6-10B cells, while inhibiting the apoptosis of these cells. Moreover, activation of ERK1/2 and Akt may be the underlying mechanism of the effects of gal-3 on NPC.

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Section: Expression Levels Of Gal-3 ---------------------------------mentioning

confidence: 99%

Galectin‑3 facilitates the proliferation and migration of nasopharyngeal carcinoma cells via activation of the ERK1/2 and Akt signaling pathways, and is positively correlated with the inflammatory state of nasopharyngeal carcinoma

Chen

Liu

et al. 2021

Mol Med Rep

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“… 48 In nasopharyngeal carcinoma, SPEN expression is also associated with lymph node metastasis and tumor stage. 49 The increased expression of SPEN was found to lead to poor prognosis, while reduced expression of SPEN suppressed migration and invasion of nasopharyngeal carcinoma. 49 These studies suggested that SPEN played an important role in tumor pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“… 49 The increased expression of SPEN was found to lead to poor prognosis, while reduced expression of SPEN suppressed migration and invasion of nasopharyngeal carcinoma. 49 These studies suggested that SPEN played an important role in tumor pathogenesis. Interestingly, both NOTCH2 and SPEN mutations were associated with lymph node metastases in our cohort.…”

Section: Discussionmentioning

confidence: 99%

<p>Mutational Characterization and Potential Prognostic Biomarkers of Chinese Patients with Esophageal Squamous Cell Carcinoma</p>

Zhang

Shi

et al. 2020

OTT

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Purpose Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China and the 5-year mortality rate is up to 70%. Studies on the ESCC genetic landscape are needed to further explore clinical therapeutic strategies. In this study, we evaluated the genetic landscape of ESCC to aid the search for clinical therapeutic strategies. Patients and Methods A total of 225 ESCC patients were enrolled in this study. Deep sequencing of 450 cancer genes was performed on formalin-fixed paraffin-embedded tumor biopsies and matched blood samples from patients. Tumor mutational burden (TMB) was calculated using an algorithm developed in-house. Results Our results showed that the most commonly mutated genes in ESCC were TP53 (96%), CCND1 (46%), FGF4 (44%), FGF19 (44%), FGF3 (44%), CDKN2A (31%), PIK3CA (26%), NOTCH1 (24%), KMT2D (18%), FAT1 (16%), and LRP1B (16%). We found that TMB correlated with patient drinking status. We identified mutations associated with sex, early ESCC, high TMB, and metastasis lymph nodes. KMT2D mutations associated with sex ( P = 0.035), tumor stage ( P = 0.016), high TMB ( P = 0.0072), and overall survival of patients ( P = 0.0026). SPEN mutations associated with high TMB ( P = 0.0016) and metastasis-positive lymph nodes ( P = 0.027). These results suggested that SPEN and KMT2D could be potential prognosis biomarkers for Chinese patients with ESCC. We also found that the number of positive lymph nodes was associated with disease-free survival. Clinical target gene analysis indicated that nearly half of Chinese ESCC patients might benefit from treatment with gene-specific target drugs. Conclusion Our study revealed the ESCC mutational landscape in 225 Chinese patients and uncovered the potential prognosis biomarker for Chinese patients with ESCC.

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“…Several studies have shown that the PI3K-Akt pathway is crucial for the proliferation, migration, and invasion of NPC cells [ 41 , 42 ]. Downregulation of the SPEN gene leads to the inactivation of PI3k-Akt and c-JUN signals, thus inhibiting the migration and invasion of NPC [ 43 ]. Zhu et al revealed that inhibition of autophagy by the ANXA1 gene may promote the migration and metastasis of NPC by activation of the PI3K-Akt pathway [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing

Zheng

et al. 2021

Cancer Cell Int

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Background Early diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC. Methods Exosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples. Results Western blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes. Conclusions We identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC.

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SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma

Cited by 23 publications

References 37 publications

Galectin‑3 facilitates the proliferation and migration of nasopharyngeal carcinoma cells via activation of the ERK1/2 and Akt signaling pathways, and is positively correlated with the inflammatory state of nasopharyngeal carcinoma

Galectin‑3 facilitates the proliferation and migration of nasopharyngeal carcinoma cells via activation of the ERK1/2 and Akt signaling pathways, and is positively correlated with the inflammatory state of nasopharyngeal carcinoma

<p>Mutational Characterization and Potential Prognostic Biomarkers of Chinese Patients with Esophageal Squamous Cell Carcinoma</p>

Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing

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