scholarly journals MBNL1 Suppressed Cancer Metastatic of Skin Squamous Cell Carcinoma Via by TIAL1/MYOD1/Caspase-9/3 Signaling Pathways

2021 ◽  
Vol 20 ◽  
pp. 153303382096075
Author(s):  
Jiaorong Chen ◽  
Jiaqi Wang ◽  
Jingyi Qian ◽  
Mengying Bao ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Caspase 3 ◽  
Underlying Mechanism ◽  
Down Regulation ◽  
Skin Squamous Cell Carcinoma ◽  
Cell Metastasis

Objective: The incidence of skin squamous cell carcinoma (SSCC) has recently been increasing, with diverse clinical manifestations.SSCC could metastasize to lymph nodes or other organs, posing a great threat to life. The present study was designed to investigate the function and underlying mechanism of muscleblind-like protein 1 (MBNL1) in skin squamous cell carcinoma. Methods: SCL-1 cell was used for vitro model and transfected with MBNL1 or siMBNL1 plasmids. MTT Assays, LDH activity ELISA, and Transwell chamber migration experiment were used to confirm the effects of MBNL1 on cell growth of SCL-1 cell. Western blot analysis was used to analyze the mechanism of MBNL1 in SCL-1 cell. Results: Down-regulation of MBNL1 promoted cell metastasis of SSCC, while up-regulation of MBNL1 reduced cell metastasis of SSCC in vitro. Down-regulation of MBNL1 suppressed the protein expression of T cell intracellular antigen (TIAL1), myogenic determinant 1 (MyoD1) and Caspase-3 in vitro. Consistent with these observations, inhibition of TIAL1 or MYOD1 expression attenuated the effects of MBNL1 in SSCC. Conclusion: The present study revealed that MBNL1 suppressed thecancer metastatic capacity of SSCC via by TIAL1/MYOD1/Caspase-3 signaling pathways.

scholarly journals LncRNA DANCR promotes the proliferation, migration, and invasion of tongue squamous cell carcinoma cells through miR-135a-5p/KLF8 axis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Zheng ◽  
Bowen Zheng ◽  
Xue Meng ◽  
Yuwen Yan ◽  
Jia He ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Ectopic Expression ◽  
Underlying Mechanism ◽  
Tongue Squamous Cell Carcinoma ◽  
Migration And Invasion

Abstract Background Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.

scholarly journals Down-Regulation of MiR-1294 is Related to Dismal Prognosis of Patients with Esophageal Squamous Cell Carcinoma through Elevating C-MYC Expression

2015 ◽  
Vol 36 (1) ◽  
pp. 100-110 ◽  
Author(s):  
Kai Liu ◽  
Liyi Li ◽  
Aizemaiti Rusidanmu ◽  
Yongqing Wang ◽  
Xiayi Lv
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Pearson Correlation ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Dismal Prognosis

Aims: Changes in the expression of microRNAs (miRNAs) have been found in many cancers. This study aimed to investigate the expression of miR-1294 in patients with esophageal squamous cell carcinoma (ESCC) and its effect on prognosis. The underlying mechanism was explored as well. Methods: We examined the expression of miRNA in human ESCC cancer tissues and adjacent non-tumor controls using quantitative reverse transcription polymerase chain reaction (qRT-PCR). And the relationship between expressions of miR-1294 and ESCC prognosis was analyzed in this study. Over-expression and knock-down methods were used to investigate the biological functions of miRNA-1294. The effect of miRNA-1294 on cell proliferation was evaluated by MTT. Besides, the function of miR-1294 on cell migration and invasion were evaluated by transwell assays. Results: MiR-1294 was significantly down-regulated in human ESCC tissues compared with the non-tumor controls tissues (P=0.014). And patients with low miR-1294 expression had a significantly poorer prognosis than those with a high miR-1294 expression (P=0.040). Negative association was defined between the expression of miR-1294 and the c-MYC expression in ESCC patients (Pearson correlation, r=-0.299, P=0.0079). Additionally, it was found that miR-1294 suppress esophageal cancer cells proliferation, migration and invasion capacity through targeting c-MYC in vitro. Conclusions: Down-regulation of miR-1294 correlates with poor prognosis of ESCC. It's partially due to the reduced function of c-MYC. This study may give insight into the understanding of pathogenesis of esophageal cancer and provide evidence for diagnosis and treatment of esophageal cancer.

scholarly journals The primary growth of laryngeal squamous cell carcinoma cells in vitro is effectively supported by paired cancer-associated fibroblasts alone

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770551 ◽  
Author(s):  
Mei Wang ◽  
Chunping Wu ◽  
Yu Guo ◽  
Xiaojuan Cao ◽  
Wenwei Zheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Laryngeal Cancer ◽  
Squamous Cell ◽  
Caspase 3 ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Carcinoma Cells ◽  
Cancer Associated Fibroblasts ◽  
Protein Levels

Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in vitro and have a low survival rate. However, in our previous work to establish a laryngeal squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts appeared to strongly inhibit the apoptosis of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In this study, we investigated whether paired laryngeal cancer-associated fibroblasts alone can effectively support the growth of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In all, 29 laryngeal squamous cell carcinoma specimens were collected and primarily cultured. The laryngeal squamous cell carcinoma cells were separated from cancer-associated fibroblasts by differential trypsinization and continuously subcultured. Morphological changes of the cultured laryngeal squamous cell carcinoma cells were observed. Immunocytofluorescence was used to authenticate the identity of the cancer-associated fibroblasts and laryngeal squamous cell carcinoma cells. Flow cytometry was used to quantify the proportion of apoptotic cells. Western blot was used to detect the protein levels of caspase-3. Enzyme-linked immunosorbent assay was used to detect the levels of chemokine (C-X-C motif) ligand 12, chemokine (C-X-C motif) ligand 7, hepatocyte growth factor, and fibroblast growth factor 1 in the supernatants of the laryngeal squamous cell carcinoma and control cells. AMD3100 (a chemokine (C-X-C motif) receptor 4 antagonist) and an anti–chemokine (C-X-C motif) ligand 7 antibody were used to block the tumor-supporting capacity of cancer-associated fibroblasts. Significant apoptotic changes were detected in the morphology of laryngeal squamous cell carcinoma cells detached from cancer-associated fibroblasts. The percentage of apoptotic laryngeal squamous cell carcinoma cells and the protein levels of caspase-3 increased gradually in subsequent subcultures. In contrast, no significant differences in the proliferation capacity of laryngeal squamous cell carcinoma cells cocultured with cancer-associated fibroblasts were detected during subculturing. High level of chemokine (C-X-C motif) ligand 12 was detected in the culture supernatant of cancer-associated fibroblasts. The tumor-supporting effect of cancer-associated fibroblasts was significantly inhibited by AMD3100. Our findings demonstrate that the paired laryngeal cancer-associated fibroblasts alone are sufficient to support the primary growth of laryngeal squamous cell carcinoma cells in vitro and that the chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 axis is one of the major contributors.

scholarly journals Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway

2019 ◽  
Vol 244 (13) ◽  
pp. 1070-1080 ◽  
Author(s):  
Hao Wu ◽  
Juanjuan Li ◽  
Jianqiu Chen ◽  
Yong Yin ◽  
Peng Da ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Exposure ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Pdx Model

The present study explored the role of LAMP3 and related molecular mechanisms in the efficacy of radiation exposure in laryngeal squamous cell carcinoma (LSCC). A lentivirus vector containing the LAMP3 gene was transfected into HEp-2 cells to construct siRNA-LAMP3 and complementation (siLAMP3+LAMP3) groups. Treatment with 4 Gy or 8 Gy radiation was administered to evaluate the role of LAMP3 in radiation therapy. Apoptosis was detected by Annexin V/propidium iodide double staining. Cell migration and invasion were measured in vitro using Transwell and Matrigel assays. Downstream genes regulated by LAMP3 were analyzed using RNA sequencing. Furthermore, a patient-derived xenograft (PDX) model of LSCC was established to verify the efficacy of radiation exposure and the associated signaling pathways downstream of LAMP3. The efficacy of radiation showed that cell proliferation was significantly inhibited by siRNA-LAMP3 knockdown. Increased apoptosis was also observed. Notably, the inhibitory effect was attenuated and apoptosis rates were decreased after LAMP3 complementation. In vitro cellular assays showed that migration and invasion were significantly suppressed by siRNA-LAMP3 knockdown and increased after LAMP3 complementation. Analysis of the efficacy of radiation exposure in the PDX model showed that LAMP3-specific knockdown inhibited tumor growth and that tumor growth was further reduced by the combined radiotherapy treatment. According to transcriptome analysis, the extracellular matrix-receptor interaction pathway is regulated by LAMP3, and further analysis revealed significant differences in key-associated molecules, including laminin subunit gamma-2 (LAMC2) and tenascin-C (TNC). Validation of the in vivo PDX model using qPCR and Western blot analyses supported the abovementioned results. The present findings suggest that reduced LAMP3 expression enhances the efficacy of radiation exposure in LSCC by regulating the LAMP3/LAMC2/TNC signaling pathway. Impact statement It is important to establish effective early diagnostic indicators and reliable treatment strategies for laryngeal squamous cell carcinoma (LSCC). We previously found that expression of LAMP3 was significantly higher in cancerous tissues compared to adjacent normal surgical margin tissues. The present study explored the role of LAMP3 and the related molecular mechanisms in the efficacy of radiation exposure in LSCC. In vitro Transwell and Matrigel assays were performed, and a patient-derived xenograft (PDX) model of LSCC was established. Associated signaling pathways downstream of LAMP3 were analyzed using RNA sequencing. Signaling pathways regulated by LAMP3 were clearly identified by combining the PDX model with transcriptome analysis. Reduced LAMP3 expression enhanced the efficacy of radiation exposure in LSCC. Thus, by utilizing this molecule as a marker, specific groups of patients may be screened for targeted therapy in the future.

scholarly journals Down-Regulation of CIDEA Promoted Tumor Growth and Contributed to Cisplatin Resistance by Regulating the JNK-p21/Bad Signaling Pathways in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Ya-Ping Gao ◽  
Lei Li ◽  
Jie Yan ◽  
Xiao-Xia Hou ◽  
Yong-Xu Jia ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Suppressor Gene ◽  
Down Regulation ◽  
Specific Pcr

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor prognosis and lack of effective targeted therapies. In this study, we investigated the tumor suppressive role of the cell death inducing DFF like effector A (CIDEA) in ESCC. Firstly, public datasets and ESCC tissue microarray analysis showed that CIDEA was frequently down-regulated at both the mRNA and protein level. This was significantly associated with low differentiation and TNM stage in ESCC, and indicated poor prognosis for ESCC patients. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) analysis revealed that the down-regulation of CIDEA was associated with hypermethylation of its promoter, which was also correlated with the poor prognosis in ESCC patients. In vitro and in vivo functional studies demonstrated that CIDEA decreased cell growth, foci formation, DNA replication, and tumorigenesis in nude mice. Further study revealed that, during starvation or cisplatin induced DNA damage, CIDEA facilitated the G1-phase arrest or caspase-dependent mitochondrial apoptosis through the JNK-p21/Bad pathway. Therefore, CIDEA is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC, and may provide a potential therapeutic target for patients with ESCC.

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