Effect of EGFR on SQSTM1 Expression in Malignancy and Tumor Progression of Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant tumor. Sequestosome 1 (SQSTM1) serves as an adaptor of autophagy for degrading protein aggregates. The regulation of autophagy by EGFR and its clinical impacts are indicated in various types of cancer. However, the association of EGFR and SQSTM1 in OSCC is still unknown. Our results show that the expression levels of SQSTM1 and EGFR proteins are higher in tumor tissues than in the corresponding tumor-adjacent (CTAN) tissues of OSCC patients. The expression levels of SQSTM1 were positively associated with the EGFR expression level. High co-expression of SQSTM1 and EGFR is associated with poor prognosis in OSCC patients. Moreover, SQSTM1 expression is decreased in EGFR-knockdown cells. Cell growth and invasion/migration are also decreased in cells with single/combined knockdowns of EGFR and SQSTM1 or in SQSTM1-knockdown cells without EGFR kinase inhibitor Lapatinib treatment compared to that in scrambled cells. However, cell growth and invasion/metastasis were not significantly different between the scrambled cells and SQSTM1-knockdown cells in the presence of Lapatinib. This study is the first to indicate the biological roles and clinical significance of SQSTM1 regulation by EGFR in OSCC.

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Map1lc3b and Sqstm1 Modulated Autophagy for Tumorigenesis and Prognosis in Certain Subsites of Oral Squamous Cell Carcinoma

Journal of Clinical Medicine ◽

10.3390/jcm7120478 ◽

2018 ◽

Vol 7 (12) ◽

pp. 478 ◽

Cited By ~ 14

Author(s):

Pei-Feng Liu ◽

Hsueh-Wei Chang ◽

Jin-Shiung Cheng ◽

Huai-Pao Lee ◽

Ching-Yu Yen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Disease Free Survival ◽

Normal Tissues ◽

Sequestosome 1 ◽

Tumor Tissues ◽

Poor Differentiation ◽

Cancer Types

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1(SQSTM1) are widely used proteins to evaluate autophagy in tumor tissues. However, the role of MAP1LC3B and SQSTM1 in OSCC is not fully understood, particularly in certain subsites. With a tissue microarray comprised of 498 OSCC patients, including 181 BMSCC, 244 TSCC, and 73 LSCC patients, we found that the expression levels of MAP1LC3B and cytoplasmic SQSTM1 were elevated in the tumor tissues of three subsites compared with those in adjacent normal tissues. MAP1LC3B was associated with a poor prognosis only in TSCC. SQSTM1 was associated with poor differentiation in three subsites, while the association with lymph node invasion was only observed in BMSCC. Interestingly, MAP1LC3B was positively correlated with SQSTM1 in the tumor tissues of BMSCC, whereas it showed no correlation with SQSTM1 in adjacent normal tissue. The coexpression of higher MAP1LC3B and SQSTM1 demonstrated a significantly worse disease-specific survival (DSS) and disease-free survival (DFS) in patients with BMSCC and LSCC, but not TSCC. The knockdown of MAP1LC3B and SQSTM1 reduced autophagy, cell proliferation, invasion and tumorspheres of BMSCC cells. Additionally, silencing both MAP1LC3B and SQSTM1 enhanced the cytotoxic effects of paclitaxel in the tumorspheres of BMSCC cells. Taken together, MAP1LC3B and SQSTM1 might modulate autophagy to facilitate tumorigenesis and chemoresistance in OSCC, particularly in BMSCC.

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PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02190-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ling Mao ◽

Xiaoweng Wu ◽

Zhengpeng Gong ◽

Ming Yu ◽

Zhi Huang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Growth ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Expression Pattern ◽

Cancer Progression ◽

Squamous Cell ◽

Aerobic Glycolysis ◽

Lactate Production ◽

Control Group

Abstract Background/objective Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC). Methods The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively. Results A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells. Conclusion This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.

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Relationship Between mir15b and Sal-Like Protein 4 and Biological Behavior of Oral Squamous Cell Carcinoma

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2548 ◽

2021 ◽

Vol 11 (2) ◽

pp. 308-314

Author(s):

Zengbo Wu ◽

Yan Yan ◽

Xianzhuo Chen ◽

Yanling Liu ◽

Dinggen Chen

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Normal Mucosa ◽

Clinicopathological Features ◽

Biological Behavior ◽

Control Group ◽

Tumor Tissues ◽

Proliferation And Invasion

miR15b and SALL4 are involved in a variety of tumor progression. The roles of miR15b and SALL4 in oral squamous cell carcinoma (OSCC) remains unclear. The tumors and normal mucosa of OSCC patients were collected to detect miR15b and SALL4 level by Real-time PCR and analyze their correlation with OSCC clinicopathological features. Oral cancer Tca8113 cells were separated into control group; miR15b mimics group and miR15b inhibitor group followed by analysis of SALL4 expression, cell survival by MTT assay; cell invasion by Transwell chamber assay, as well as expression of N-cadherin and Vimentin and correlated with TNM stage, tumor volume and metastasis, and positively with differentiation TGF-β by Western blot. miR15b expression was decreased and SALL4 expression was increased in OSCC tumor tissues. miR15b was negatively degree (P < 0.05), whereas, opposite correlation of SALL4 with the above parameters was found (P < 0.05). miR15b and SALL4 were negatively correlated. MiR15b mimics significantly up-regulated MiR15b, decreased SALL4 expression, inhibited Tca8113 cell proliferation and invasion, as well as reduced N-cadherin, Vimentin and TGF-βexpression (P < 0.05). Opposite results were found in MiR15b inhibitor group. MiR15b expression is decreased and SALL 4 is increased in OSCC tumor tissues. MiR15b and SALL4 is closely related to OSCC clinicopathological features. MiR15b regulates the expression of EMT-related genes and TGF-β, thereby altering the proliferation and invasion of OSCC cells.

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Long non-coding RNA C5orf66-AS1 prevents oral squamous cell carcinoma through inhibiting cell growth and metastasis

International Journal of Molecular Medicine ◽

10.3892/ijmm.2018.3913 ◽

2018 ◽

Cited By ~ 2

Author(s):

Tianzhu Lu ◽

Hongjing Liu ◽

Ganhua You

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Growth ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Non Coding Rna ◽

Long Non Coding Rna

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Salivary LDOC1 is a gender-difference biomarker of oral squamous cell carcinoma

PeerJ ◽

10.7717/peerj.6732 ◽

2019 ◽

Vol 7 ◽

pp. e6732 ◽

Cited By ~ 2

Author(s):

Chung-Ji Liu ◽

Jen-Hao Chen ◽

Shih-Min Hsia ◽

Chiu-Chu Liao ◽

Hui-Wen Chang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Suppressor Gene ◽

Clinicopathological Characteristics ◽

Pcr Analysis ◽

Expression Levels ◽

Low Levels

Background The X-linked tumor suppressor gene LDOC1 is reported to be involved in oral cancer. The detection of biomarkers in salivary RNA is a non-invasive strategy for diagnosing many diseases. The aim of the present study was to investigate the potential of salivary LDOC1 as a biomarker of oral cancer. Methods We determined the expression levels of LDOC1 in the saliva of oral squamous cell carcinoma (OSCC) subjects, and investigated its correlation with various clinicopathological characteristics. The expression levels of salivary LDOC1 were detected in 53 OSCC subjects and 43 healthy controls using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. We used Fisher’s exact test to analyze the correlations between expression levels and clinicopathological characteristics. Results Salivary LDOC1 was significantly upregulated in females with OSCC (p = 0.0072), and significantly downregulated in males with OSCC (p = 0.0206). Eighty-nine percent of male OSCC subjects who smoked expressed low levels of LDOC1. OSCC cell lines derived from male OSCC subjects expressed low levels of LDOC1. Conclusions A high level of salivary LDOC1 expression is a biomarker of OSCC in females. A high percentage of male OSCC subjects who smoke express low levels of salivary LDOC1. A low level of salivary LDOC1 expression is a biomarker of OSCC in males.

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