LncRNA LEF1-AS1 regulates proliferation, apoptosis, migration and invasion of cutaneous squamous cell carcinoma cells by targeting miR-612: an in vitro experimental study

Abstract BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Increasing evidence has revealed that Human Papillomavirus (HPV) infection may be associated with the possible etiology of ESCC. Nevertheless, the precise role of HPV in ESCC remains unclear.MethodsProliferation and apoptosis capability of ESCC cells upon infection of HPV16 E6 were detected by CCK-8 assay and Western blotting analysis. Wound healing assay and Transwell experiment were conducted to determine the ability of migration and invasion, and the mRNA expression of E6AP, p53, miR-34a was determined by real-time PCR after transfected with HPV16 E6 plasmid. ResultsIn ESCC cells, the ability of proliferation, migration and invasion were increased, and the ability of apoptosis was decreased after transfected with HPV16 E6 plasmid. Furthermore, the mRNA level of E6AP, P53 and miR-34a were decreased in HPV16 E6-transfected cell lines.ConclusionsOur results not only provide evidence that in ESCC, HPV16 E6 promotes cell proliferation, migration and invasion, inhibits cell apoptosis, but also suggest that there may be a correlation between E6AP, P53 and miR-34a in HPV-transfected cell lines. These findings indicated that HPV16 E6 may play an important role in the development of ESCC.

Download Full-text

Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666181029170605 ◽

2019 ◽

Vol 19 (2) ◽

pp. 248-255 ◽

Cited By ~ 2

Author(s):

Ling Gao ◽

Jianwei Dong ◽

Nanyang Zhang ◽

Zhanxian Le ◽

Wenhao Ren ◽

...

Keyword(s):

Cell Cycle ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cyclosporine A ◽

Migration And Invasion ◽

Signal Molecules ◽

Cox 2

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

Download Full-text

Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

International Journal of Oral Science ◽

10.1038/s41368-021-00118-4 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Wen Chen ◽

Chenzhou Wu ◽

Yafei Chen ◽

Yuhao Guo ◽

Ling Qiu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Endoplasmic Reticulum ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Endoplasmic Reticulum Stress ◽

Cell Carcinoma ◽

Squamous Cell ◽

Migration And Invasion ◽

Ceramide Synthase

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

Download Full-text

Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

Integrative Cancer Therapies ◽

10.1177/15347354211031646 ◽

2021 ◽

Vol 20 ◽

pp. 153473542110316

Author(s):

Liang Wang ◽

Lei Xu ◽

Yu Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Dna Methyltransferase ◽

Cutaneous Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Dependent Manner ◽

Concentration Gradients ◽

A431 Cells

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.

Download Full-text

THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-03690-z ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Jiwei Cheng ◽

Haibo Ma ◽

Ming Yan ◽

Wenqun Xing

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Positive Feedback ◽

Feedback Loop ◽

Malignant Tumors ◽

Migration And Invasion ◽

Positive Feedback Loop

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the digestive system with a high incidence and poor prognosis. Long non-coding RNAs (LncRNA) have been reported to be closely associated with the occurrence and development of various human cancers. Data from GSE89102 shows an increase of THAP9-AS1 expression in ESCC. However, its functions and mechanisms underlying ESCC progression remain to be investigated. In this study, we found that THAP9-AS1 was overexpressed in ESCC tissues and cells. High THAP9-AS1 expression was positively correlated with tumor size, TNM stage, lymph node metastasis, and worse prognosis. Functionally, depletion of THAP9-AS1 suppressed cell proliferation, migration, and invasion, while enhanced apoptosis in vitro. Consistently, knockdown of THAP9-AS1 inhibited xenograft tumor growth in vivo. Mechanistically, THAP9-AS1 could serve as a competing endogenous RNA (ceRNA) for miR-133b, resulting in the upregulation of SOX4. Reciprocally, SOX4 bound to the promoter region of THAP9-AS1 to activate its transcription. Moreover, the anti-tumor property induced by THAP9-AS1 knockdown was significantly impaired due to miR-133b downregulation or SOX4 overexpression. Taken together, our study reveals a positive feedback loop of THAP9-AS1/miR-133b/SOX4 to facilitate ESCC progression, providing a potential molecular target to fight against ESCC.

Download Full-text