scholarly journals LncRNA HOXA-AS2 Promotes Oral Squamous Cell Proliferation, Migration, and Invasion via Upregulating EZH2 as an Oncogene

2021 ◽  
Vol 20 ◽  
pp. 153303382110391
Author(s):  
Zhen Zhao ◽  
Yan Xing ◽  
Fei Yang ◽  
Zhijun Zhao ◽  
Yupeng Shen ◽  
...  

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) serve important roles in the development of OSCC. The purpose of this study was to investigate the biological function and underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) in OSCC. RT-qPCR was performed to analyze the HOXA-AS2 expressions in human immortalized oral epithelial cell (HIOEC) line, human OSCC cell lines, and plasma. The expression of HOXA-AS2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in Tca-8113 cells were knocked down or overexpressed by transfection with shRNA-HOXA-AS2 or pcDNA-EZH2, respectively. The interaction between HOXA-AS2 and EZH2 was validated by RNA immunoprecipitation assay. In addition, cell proliferation was assessed by CCK-8 and EdU assays. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion were detected using wound healing and Transwell assays, respectively. Apoptosis was detected by TUNEL staining. The protein expression levels of cell cycle and apoptosis-related proteins were measured by western blot analysis. Compared with HIOEC cells, HOXA-AS2 expression in OSCC cells was upregulated. HOXA-AS2 knockdown significantly inhibited Tca-8113 cell proliferation, blocked the cell cycle by arresting cells in the G0/G1 phase, promoted apoptosis, and suppressed migration and invasion. In addition, HOXA-AS2 was predicted to directly target EZH2 and positively regulate EZH2 expression. EZH2 overexpression could reverse the inhibitory effect of HOXA-AS2 knockdown on the proliferation, migration, and invasion of Tca-8113 cells. In summary, the findings suggested that HOXA-AS2 may inhibit cell proliferation, invasion, and migration, induce cell cycle arrest in the G0/G1 phase, and increase cell apoptosis by targeting EZH2. The research indicated that HOXA-AS2/EZH2 axis may play a key role in the development of OSCC.

Author(s):  
Xiali Tang ◽  
Ying Zheng ◽  
Demin Jiao ◽  
Jun Chen ◽  
Xibang Liu ◽  
...  

Background: Small Cell Lung Cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. The purpose of this study was to investigate the effect of anlotinib on SCLC and the potential molecular mechanisms. Methods: Cell viability was assessed by CCK-8 assay to determine the adequate concentration of anlotinib. Then, effects of anlotinib on cell apoptosis, cell cycle distribution, migration and invasion were analyzed by flow cytometry, PI staining, wound healing assay and transwell assay, respectively. The protein expression of c-met and ERK1/2 pathways in H446 cells were assessed by western blot analysis. Result: In this study, we found that anlotinib significantly reduced the cell viability of H446 cells, induced G2/M cell cycle arrest and decreased invasion and migration of H446 cells. Futhermore, we also found that anlotinib could suppress c-met signal transduction and activate the ERK1/2 pathway in H446 cells. More importantly, c-met was involved in the effects of anlotinib on migration and invasion in H446 cells. Conclusion: Taken together, our results demonstrated that anlotinib was a potential anticancer agent that inhibited cell proliferation, migration and invasion via suppression of the c-met pathway and activation of the ERK1/2 pathway in H446 cells.


2018 ◽  
Vol 19 (7) ◽  
pp. 2029 ◽  
Author(s):  
Xiaoqi Zhang ◽  
Hao Feng ◽  
Ziyu Li ◽  
Jie Guo ◽  
Minqi Li

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. In China, its 5-year survival rate is roughly 50%, owing to acquired chemotherapeutic resistance and metastasis of the disease. Accumulating evidence demonstrates that aspirin (ASA) acts as a preventive or therapeutic agent in multiple cancers; however, anti-tumor activities induced by aspirin are unclear in OSCC. To investigate the possible role of aspirin in OSCC development, we first employed bioinformatics to analyze the anti-OSCC effects of aspirin. We performed a genetic oncology (GO) enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and the protein–protein interaction (PPI) network analysis by Cytoscape for differentially expressed genes (DEGs). We also evaluated the potential effects of aspirin on cell proliferation, invasion, migration, and apoptosis in two well-characterized OSCC cell lines (TCA8113 and CAL27). The bioinformatic results revealed that aspirin could inhibit proliferation by blocking the cell cycle, and could reduce migration and invasion via the PI3K-Akt and focal adhesion pathways. We found that ASA could downregulate the OSCC cell proliferation colony formation, invasion, and migration, as well as upregulate apoptosis. Furthermore, we found that ASA suppressed the activation of the focal adhesion kinase (FAK) and the phosphorylation of Akt, NF-κB, and STAT3. Overall, our data suggested that ASA may be developed as a chemopreventive agent to effectively treat OSCC.


2020 ◽  
Author(s):  
Yuan Xu ◽  
Yuhuan Jia ◽  
Liang Chen ◽  
Jing Gao ◽  
Deqin Yang

Abstract Background: Streptococcus anginosus(S.anginosus) was reported increased in oral squamous cell carcinoma(OSCC) tissue. The aim of this study was to investigate the response of oral cancer cells in the biological characteristics evoked by the S.anginosus and investigate its potential mechanisms.Methods: The growth curve and concentration standard curve of S.anginosus were determined , and a series of concentrations of S.anginosus supernatant were applied to OSCC cell lines SCC15,then selected an optimal time and concentration by CCK-8 assay. Then autophagic response, proliferative activity, cell cycle and apoptosis, invasion and migration abilities were evaluated in SCC15.Results: The results showed that when the ratio of S.anginosus supernatant to cell culture medium was 1:1 and the co-culture time was 16h, there was a most significant inhibited effect on SCC15; Furthermore, S.anginosus supernatant can up-regulate the autophagy activity of SCC15, then, the ability of proliferation, migration and invasion was observed inhibited obviously. Compared with the control groups, the cell cycle showed G1 arrest, S and G2 / M phases decreased, and the percentage of apoptotic cells relatively increased(P<0.05).Conclusion: S.anginosus can reduce the proliferation, migration and invasion of SCC15 cells and promote cell apoptosis; Moreover, autophagy may be one of the mechanisms in this process.


Author(s):  
Yi Miao ◽  
Meng Lu ◽  
Qin Yan ◽  
Shuangdi Li ◽  
Youji Feng

Pyruvate kinase (PK) is a key enzyme in the process of glycolysis, catalyzing phosphoenolpyruvate (PEP) into pyruvate. Currently, PK isozyme type M2 (PKM2), one subtype of PK, has been proposed as a new tumor marker with high expression in various tumor tissues. Here we aimed to explore the effects of siRNA-PKM2 on ovarian carcinoma (OC) cell lines SKOV3 and OVCAR3, in which PKM2 was notably expressed. PKM2 gene interference lentivirus vectors were built by miRNA transfection assay. siRNA-PKM2-transfected SKOV3 and OVCAR3 cells were evaluated for cell proliferation, cell cycle distribution, cell apoptosis, cell migration, and invasion in this study. In addition, the expression levels of several tumor-related genes were measured using real-time PCR and Western blot. Results showed that siRNA-PKM2 markedly inhibited cell proliferation, induced apoptosis, and caused cell cycle arrest at the G0/G1 phase. Cell migration and invasion were significantly suppressed by siRNA-PKM2. Furthermore, the tumor-related genes caspase 7, Bad, and E-cadherin were upregulated, while MMP2, HIF1α, VEGF, and MMP9 were depressed by siRNA-PKM2. The function of siRNA-PKM2 on the biological behavior of OC cells indicated that PKM2 may also be a target for treatment of OC.


2021 ◽  
Author(s):  
Lixia Fan ◽  
Wanqin Liao ◽  
Zezhen Chen ◽  
Shaojing Li ◽  
Anping Yang ◽  
...  

Abstract BackgroundRelapse and drug resistance of lymphomas are common, howerver the treatment efficacy of current therapeutic strategies remains unsatisfied. Our current study revealed that the extract of Ophiorrhiza pumila (OPE) has a potential anti-liver cancer activity. In this study, we aimed to investigate the effect of OPE on preventing lymphomas and explored the underlying mechanisms.MethodsCCK-8 assay was applied to detect the effect of OPE on cell proliferation. Flow cytometry was used to analyzed the effect of OPE on cell cycle distribution, and apoptosis. Xenograft mouse model was conducted to determine the anti-tumor activity of OPE. TNUEL assay was performed to detect the apoptosis in tumor tissues. Western blot and immunohistochemistry were used to determined protein expression.ResultsOPE decreased A20 cell proliferation in a dose- and time-dependent manner. OPE treatment induced cell cycle arrest at S phase and elevated apoptosis in A20 cells. Moreover, OPE displayed a significant inhibition in tumor growth in a mouse model. OPE increased apoptosis in tumor tissues revealed by TUNEL assay, which was companied with enhanced cleaved caspase 3 expression and Bax/Bcl2 ratio. In addition, our data showed that OPE suppressed A20 cell viability partially by reducing EGFR phosphorylation.ConclusionsOur data showed that OPE has an inhibitory effect on A20 cell proliferation and tumor growth, which is mediated by inactivation of EGFR and enhanced apoptosis.


2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Yice Xu ◽  
Qingyuan Zhang ◽  
Jie Zhou ◽  
Zhaolong Li ◽  
Junyu Guo ◽  
...  

AbstractLaryngeal carcinoma is one of the most common malignant tumors of the head, neck, and respiratory tract. The aim of the present study is to explore the biological function of SRY-related HMG-box 18 (SOX18) in laryngeal carcinoma cells and study the molecular mechanism involved. Initial findings indicate that the expression of SOX18 was increased in laryngeal carcinoma cell lines and tissues. The effect of SOX18 on laryngeal carcinoma cell proliferation, cell cycle, apoptosis, invasion, and migration was also identified. The results indicated that down-regulation of SOX18 significantly inhibited cell proliferation, migration, and invasion, and induced cell-cycle arrest in G0/G1 phase and apoptosis of laryngeal carcinoma cells. However, overexpression of SOX18 promoted cell proliferation, invasion, and migration, and inhibited cell apoptosis. The expression of cyclin D1, active-caspase-3, N-cadherin, MTA1, MMP-2, and MMP-7 was also regulated by the overexpression of siSOX18 or SOX18. In addition, it was found that SOX18 could also accelerate the phosphorylation of JAK2/STAT3 signaling in laryngeal carcinoma cells. Furthermore, our study indicated that SOX18 could stimulate cell proliferation, migration, and invasion of laryngeal carcinoma cells via regulation of JAK2/STAT3 signaling, which could provide a new strategy for laryngeal carcinoma diagnosis and molecular therapies.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuan Xu ◽  
Yuhuan Jia ◽  
Liang Chen ◽  
Jing Gao ◽  
DeQin Yang

Abstract Background Streptococcus anginosus (S. anginosus) was reported increased in oral squamous cell carcinoma (OSCC) tissue. The aim of this study was to investigate the response of oral cancer cells in the biological characteristics evoked by the S. anginosus and investigate its potential mechanisms. Methods The growth curve and concentration standard curve of S. anginosus were determined, and a series of concentrations of S. anginosus supernatant were applied to OSCC cell lines SCC15, then selected an optimal time and concentration by CCK-8 assay. Then autophagic response, proliferative activity, cell cycle and apoptosis, invasion and migration abilities were evaluated in SCC15. Results The results showed that when the ratio of S. anginosus supernatant to cell culture medium was 1:1 and the co-culture time was 16 h, the inhibitory effect on SCC15 was the most obvious; Furthermore, the supernatant of Streptococcus upregulated the autophagy activity of SCC15, thus significantly inhibiting its proliferation, migration and invasion ability. Compared with control groups, the cell cycle showed G1 arrest, S and G2/M phases decreased, and the percentage of apoptotic cells relatively increased (P < 0.05). Conclusion S. anginosus reduced the proliferation, migration and invasion of SCC15 cells and promoted cell apoptosis; Moreover, autophagy may be one of the mechanisms in this process.


2021 ◽  
Author(s):  
Yuan Xu ◽  
Yuhuan Jia ◽  
Liang Chen ◽  
Jing Gao ◽  
Deqin Yang

Abstract Background: Streptococcus anginosus(S.anginosus) was reported increased in oral squamous cell carcinoma(OSCC) tissue. The aim of this study was to investigate the response of oral cancer cells in the biological characteristics evoked by the S.anginosus and investigate its potential mechanisms.Methods: The growth curve and concentration standard curve of S.anginosus were determined , and a series of concentrations of S.anginosus supernatant were applied to OSCC cell lines SCC15,then selected an optimal time and concentration by CCK-8 assay. Then autophagic response, proliferative activity, cell cycle and apoptosis, invasion and migration abilities were evaluated in SCC15.Results: The results showed that when the ratio of S.anginosus supernatant to cell culture medium was 1:1 and the co-culture time was 16h, the inhibitory effect on SCC15 was the most obvious; Furthermore, the supernatant of Streptococcus upregulated the autophagy activity of SCC15, thus significantly inhibiting its proliferation, migration and invasion ability. Compared with control groups, the cell cycle showed G1 arrest, S and G2 / M phases decreased, and the percentage of apoptotic cells relatively increased(P<0.05).Conclusion: S.anginosus reduced the proliferation, migration and invasion of SCC15 cells and promoted cell apoptosis; Moreover, autophagy may be one of the mechanisms in this process.


2020 ◽  
Author(s):  
Yuan Xu ◽  
Yuhuan Jia ◽  
Liang Chen ◽  
Jing Gao ◽  
Deqin Yang

Abstract Background: Streptococcus anginosus(S.anginosus) was reported increased in oral squamous cell carcinoma(OSCC) tissue. The aim of this study was to investigate the response of oral cancer cells in the biological characteristics evoked by the S.anginosus and investigate its potential mechanisms.Methods: The growth curve and concentration standard curve of S.anginosus were determined , and a series of concentrations of S.anginosus supernatant were applied to OSCC cell lines SCC15,then selected an optimal time and concentration by CCK-8 assay. Then autophagic response, proliferative activity, cell cycle and apoptosis, invasion and migration abilities were evaluated in SCC15.Results: The results showed that when the ratio of S.anginosus supernatant to cell culture medium was 1:1 and the co-culture time was 16h, there was a most significant inhibited effect on SCC15; Furthermore, S.anginosus supernatant can up-regulate the autophagy activity of SCC15, then, the ability of proliferation, migration and invasion was observed inhibited obviously. Compared with the control groups, the cell cycle showed G1 arrest, S and G2 / M phases decreased, and the percentage of apoptotic cells relatively increased(P<0.05).Conclusion: S.anginosus can reduce the proliferation, migration and invasion of SCC15 cells and promote cell apoptosis; Moreover, autophagy may be one of the mechanisms in this process.


2020 ◽  
Author(s):  
Zhen Zhao ◽  
Yan Xing ◽  
Fei Yang ◽  
Zhijun Zhao ◽  
Yupeng Shen ◽  
...  

Abstract Background Oral squamous cell carcinoma (OSSC) is one of the most common cancers in the world. The aim to the study was to evaluated the biological function and partly underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) on oral squamous cell carcinoma. Methods The expression of HOXA-AS2 in OSSC cells was detected by quantitative real time polymerase chain reaction (qRT-PCR). HOXA-AS2 expression was modified by transfection with HOXA-AS2 knockdown into TCA-8113 cells. The biological activity of TCA-8113 cells were detected by Cell Counting Kit-8 (CCK-8), EdU staining, Tunel staining, flow cytometry, wound healing, transwell assasy and western blot. The relationship between HOXA-AS2 and EZH2 was analyzed by RNA immunoprecipitation (RIP). Results At first, in this study, HOXA-AS2 expression in TCA-8113 cell line was increased compared with normal oral cells. Furthermore, HOXA-AS2 knockdown could inhibit cell viability, migration and invasion. Besides, EZH2 is the target of HOXA-AS2 in TCA-8113 cells. EZH2 expression was reduced by the HOXA-AS2 knockdown and the expression of P21 was negatively correlated to the expression of HOXA-AS2 in TCA-8113 cells. Conclusion In this study, silencing HOXA-AS2 reduced cell viability, invasion and migration capacity and EZH2, as an oncogene, could be downregulated by HOXA-AS2 knockdown in OSSC cells.


Sign in / Sign up

Export Citation Format

Share Document