2.Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma.
Xiaochen WANG ; Kang LI ; Yuehan WAN ; Fangfang CHEN ; Maosheng CHENG ; Gan XIONG ; Ganping WANG ; Shuang CHEN ; Zhi CHEN ; Jianwen CHEN ; Xiuyun XU ; Cheng WANG ; Liang PENG ; Demeng CHEN
International Journal of Oral Science 2021;13(1):26-26
Methyltransferase like 13 (METTL13), a kind of methyltransferase, is implicated in protein binding and synthesis. The upregulation of METTL13 has been reported in a variety of tumors. However, little was known about its potential function in head and neck squamous cell carcinoma (HNSCC) so far. In this study, we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level. Increased METTL13 was negatively associated with clinical prognosis. And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro. Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail, the key transcription factor in EMT, hence regulating the progression of EMT. Furthermore, Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes. Altogether, our study had revealed the oncogenic role of METTL13 in HNSCC, and provided a potential therapeutic strategy.
Head and Neck Neoplasms
;
Humans
;
Squamous Cell Carcinoma of Head and Neck/genetics*
3.Gene mutations of esophageal squamous cell carcinoma based on next-generation sequencing.
Long WANG ; Yi-Meng JIA ; Jing ZUO ; Yu-Dong WANG ; Zhi-Song FAN ; Li FENG ; Xue ZHANG ; Jing HAN ; Wen-Jing LYU ; Zhi-Yu NI
Chinese Medical Journal 2021;134(6):708-715
BACKGROUND:
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression.
METHODS:
Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis.
RESULTS:
The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05).
CONCLUSION
Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.
B7-H1 Antigen
;
Carcinoma, Squamous Cell/genetics*
;
Esophageal Neoplasms/genetics*
;
Esophageal Squamous Cell Carcinoma/genetics*
;
High-Throughput Nucleotide Sequencing
;
Humans
;
Mutation/genetics*
5.MicroRNA in head and neck carcinoma.
Chinese Journal of Pathology 2013;42(5):355-358
6.Clinicopathological features of verrucous type dysplasia of esophagus.
Wei Hua HOU ; Shu Jie SONG ; Wei Dong HOU ; Zhong Yue SHI ; Li Juan MA ; Jing Wei NIU ; Mu Lan JIN
Chinese Journal of Pathology 2022;51(12):1217-1222
Objective: To investigate the clinicopathological features of verrucous type (squamous) dysplasia of esophagus. Methods: The clinicopathological data of 18 verrucous type dysplasia of esophagus patients in the 989th Hospital of the Joint Logistics Support Force of the People's Liberation Army (formerly 152 Central Hospital) and Beijing Chaoyang Hospital Affiliated to Capital Medical University from 2009 to 2021 were retrospectively collected. The histomorphologic characteristics and immunophenotype were observed, and human papillomavirus (HPV) genotyping was detected by PCR-fluorescence probe. The relevant literature was reviewed. Results: The median age of the 18 patients was 68 years (range 53-76 years); there were 13 males and 5 females. There were four cases in the upper esophagus, seven in the middle esophagus and seven in the lower esophagus. The median diameter of the lesion was 18 mm (range 6-54 mm). According to the Paris Classification, 11 cases were 0-Ⅱa, one case was 0-Ⅱa+Ⅰ, five cases were 0-Ⅱb, and one case was 0-Ⅱb+Ⅰ. White light endoscopy showed that the surface of the lesion was white plaque, red areas between the plaques, and papillary surface structure could be seen. In narrow-band imaging, some mucosal areas of lesions were opaque or patchy and light brown, and papillary microsurface structures were different in shapes and sizes. Intraepithelial microvessels were elongated, dilated, twisted and varied in diameter. Lugol iodine stain showed nil to faint staining. Histologically, the atypia cells were large with rounded to irregular nuclei, coarse chromatin, mitotic figures, and abundant eosinophilic cytoplasm. The basal cells showed increased atypia, crowding, increased nuclear-cytoplasmic ratio, and active mitosis. The cells were arranged haphazardly. Single cell keratinization, binuclear cells, and hollow-out-like cells, as well as surface epithelial keratinization and parakeratosis were observed in three cases. There were obvious verrucous or papillary structures in the epithelial layer. Five patients had local verrucous carcinoma. Immunohistochemical staining showed that the mutant expression of p53 protein in 6/10 cases; p16 was positive in 5/10 cases; abnormal Ki-67 distribution pattern in 10/10 cases. HPV was negative in all 10 cases tested. The original pathologic diagnosis of preoperative biopsy was high-grade dysplasia in 8 cases, low-grade dysplasia in 6 cases and atypical squamous epithelial cells in 4 cases. Conclusions: Esophageal verrucous dysplasia tumor cells are well differentiated with obvious verrucous or papillary structures. The unique morphological features suggest that it represents a histological subtype of esophageal squamous high-grade dysplasia and it is a precursor of verrucous carcinoma. Its preoperative biopsy diagnosis is challenging.
Humans
;
Middle Aged
;
Aged
;
Papillomavirus Infections
;
Retrospective Studies
;
Carcinoma, Verrucous/genetics*
;
Carcinoma, Squamous Cell
7.circ_0005379 inhibits the progression of oral squamous cell carcinoma by regulating the miR-17-5p/acyl-CoA oxidase 1 axis.
Hai-Xia ZHOU ; Lu-Yao WANG ; Shuai CHEN ; Dan-Dan WANG ; Zheng FANG
West China Journal of Stomatology 2021;39(4):425-433
OBJECTIVES:
To investigate the effects of circ_0005379 on the proliferation, apoptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) cells and its mechanism.
METHODS:
Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of circ_0005379 and miR-17-5p in OSCC tissues and SCC15 cell lines. Western blot was used to detect the expression levels of acyl-CoA oxidase 1 (ACOX1). The circ_0005379 overexpression vector was transfected into SCC15 cells. Methyl thiazolyl tetrazolium blue staining, flow cytometry, Transwell, and Western blot were used to detect the effects of circ_0005379 overexpression on the proliferation, apoptosis, migration, and invasion of SCC15 cells and the expression of E-cadherin, β-catenin, and Snail proteins. Dual luciferase reporter assay and RNA immunoprecipitation were used to examine the regulation of circ_0005379, miR-17-5p, miR-17-5p, and ACOX1 in SCC15 cells. A nude mouse xenograft model of SCC15 cells stably overexpressing circ_0005379 was established, and the effect of circ_0005379 overexpression on the growth of xenografts in nude mice was observed.
RESULTS:
Compared with adjacent cancer tissues, the expression levels of circ_0005379 and ACOX1 proteins in OSCC tissues were decreased (
CONCLUSIONS
circ_0005379 may inhibit the proliferation, migration, and invasion of OSCC cells by downregulating the expression of miR-17-5p and upregulating ACOX1, which promote apoptosis and inhibit tumor growth
Acyl-CoA Oxidase
;
Animals
;
Carcinoma, Squamous Cell/genetics*
;
Cell Proliferation
;
Head and Neck Neoplasms
;
Humans
;
Mice
;
Mice, Nude
;
MicroRNAs
;
Mouth Neoplasms/genetics*
;
RNA, Circular
;
Squamous Cell Carcinoma of Head and Neck
8.Gene expression profile changes in oral verrucous carcinoma and oral squamous cell carcinoma.
Zhan-gui TANG ; Su-ping ZHAO ; Lei ZHANG ; Xiao-ling LI
Chinese Journal of Stomatology 2007;42(4):229-230
OBJECTIVETo determine the difference in the gene expression between human oral verrucous carcinoma (OVC) and oral squamous cell carcinoma (OSCC).
METHODScDNA chip was used to detect the mRNA of cancer tissue from 4 OVC and 4 OSCC. After profile blotted and handled by bioinformation, the gene expression of these two kinds of lesions was examined.
RESULTSUsing the BioStarH-40 profile, 593 different expression of genes was found. The rate of different genes was 15.2%, of which the expression of 283 genes increased (59 genes significantly increased) and 310 genes decreased (98 genes significantly decreased) in OVC tissue than that in OSCC.
CONCLUSIONSThe gene expression of OVC and OSCC was different, which many contribute to the different biological behavior of these two kinds of lesions.
Carcinoma, Squamous Cell ; genetics ; Carcinoma, Verrucous ; genetics ; Gene Expression Profiling ; Humans ; Mouth Neoplasms ; genetics ; Oligonucleotide Array Sequence Analysis
9.LINC00668 is Highly Expressed in Lung Squamous Cell Carcinoma and Promotes Tumor Cell Migration and Invasion.
Bo YUAN ; Yang CHEN ; Jingyan YUAN ; Lizhong ZENG ; Shuanying YANG
Chinese Journal of Lung Cancer 2022;25(4):226-235
BACKGROUND:
A lack of effective treatment for lung squamous cell carcinoma (LUSC) makes it an important factor restricting the 5-year survival rate of non-small cell lung cancer (NSCLC). Long non-coding RNA 00668 (LINC00668) was reported to play crucial regulatory roles in the tumorigenesis and progression of various cancers; however, its role in LUSC is unclear. The aim of this study was to investigate the prognosis value and biological function of LINC00668 in NSCLC, especially in LUSC.
METHODS:
The expression pattern of LINC00668 and its relationship with clinical characteristics and prognosis of patients were investigated in the NSCLC especially LUSC based on The Cancer Genome Altas (TCGA) database. Its function in LUSC cells was explored in vitro.
RESULTS:
LINC00668 expression was significantly up-regulated in LUSC patients and high expression level of LINC00668 was associated with advanced tumor-node-metastasis (TMN) stage. Moreover, the expression of LINC00668 significantly increased in smoking patients, and was a prognostic indicator for overall survival (OS) of smoking patients with LUSC. In vitro experiments showed that LINC00668 has significantly higher expression level in LUSC cell lines and tissues compared to normal bronchial epithelial cell and para-tumor tissues; meanwhile, functional assay indicated knockdown of LINC00668 effectively inhibited the migration and invasion of LUSC cells.
CONCLUSIONS
LINC00668 might closely relate to the development of LUSC, and inhibition of LINC00668 may reduce the metastasis of LUSC.
Carcinoma, Non-Small-Cell Lung
;
Carcinoma, Squamous Cell/genetics*
;
Cell Movement/genetics*
;
Humans
;
Lung
;
Lung Neoplasms/genetics*
;
RNA, Long Noncoding/genetics*
10.Oncogene expressions detected by in situ hybridization of squamous metaplasia, dysplasia and primary lung cancer in human.
Jung Dal LEE ; Dong Hoo LEE ; Sung Soo PARK ; Dong Ho SHIN ; Hyo Chul CHUNG ; Jung Hee LEE
Journal of Korean Medical Science 1989;4(3):121-127
In order to elucidate the dynamic changes of oncogene expression in the sequential cascade of squamous metaplasia, dysplasia, and squamous cell carcinoma of the bronchial epithelium, hybridization in situ was employed with a biotinylated oncogene probe. The expression of c-myc was localized exclusively in nuclei. While normal bronchial epithelium revealed no discernible clumps of c-myc grains, except occasional grains less than 3 per cell, squamous metaplasia showed increased number of grains and a few clusters of c-myc grains. In dysplasia, c-myc expression was more intensive than in squamous metaplasia. Approximately, 1/3 to 2/3 of tumor cell populations of squamous cell carcinomas of the lung revealed tremendously increased c-myc expression. In addition clumpy grains of c-myc in squamous cell carcinoma appeared more frequently than in squamous metaplasia or dysplasia. The c-myc expression was found to vary between different samples and within each cancer, and not all cancer cells expressed c-myc. These data indicate that c-myc oncogene plays it's role on reprogramming for growth control of cell populations particularly in multistage carcinogenesis and progression of lung cancer. These dynamic alterations of c-myc expression suggest that neoplastic transformation may occur conceivably at the dysplastic phase eventually resulting in carcinoma in situ. This means, in turn, squamous dysplasia is a putative precancerous lesion of the human lung.
Bronchial Neoplasms/*genetics/pathology
;
Carcinoma, Squamous Cell/*genetics/pathology
;
Cell Transformation, Neoplastic/*genetics
;
DNA
;
Humans
;
Metaplasia
;
Nucleic Acid Hybridization
;
*Oncogenes