LncRNA SNHG17 promotes the progression of oral squamous cell carcinoma by modulating miR-375/PAX6 axis

BACKGROUND: The prognosis of patients with recurrent and/or metastatic oral squamous cell carcinoma (OSCC) remains poor, and its incidence is especially high in developing countries. Multiple long non-coding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. This study aimed to probe into the role of lncRNA small nucleolar RNA host gene 17 (SNHG17) on the progression of OSCC. METHODS: The expression level of SNHG17 in OSCC samples was tested using quantitative real-time polymerase chain reaction (qRT-PCR). Human OSCC cell lines CAL-27 and Tca8113 were used in in vitro studies. Cell counting kit-8 (CCK-8) and BrdU assays were used to assess the effect of SNHG17 on OSCC cell proliferation. Flow cytometry was used to study the effect of SNHG17 on OSCC cell apoptosis. Transwell assay was conducted to detect the effect of SNHG17 on migration and invasion. Moreover, luciferase reporter assay was employed to confirm targeting relationship between miR-375 and SNHG17. Additionally, Western blot was used to observe the regulatory function of SNHG17 on PAX6. RESULTS: SNHG17 expression in OSCC clinical samples was significantly increased and was correlated with unfavorable pathological indexes. Its overexpression remarkably accelerated proliferation and metastasis of OSCC cells, while reduced apoptosis. Accordingly, knockdown of SNHG17 suppressed the malignant phenotypes of OSCC cells. Overexpression of SNHG17 significantly reduced the expression of miR-375 by sponging it, but enhanced the expression of PAX6. CONCLUSION: SNHG17 is a sponge of tumor suppressor miR-375 in OSCC, enhances the expression of PAX6 indirectly, and functions as an oncogenic lncRNA.

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Long Non-Coding RNA CCAT2 Promotes the Development of Esophageal Squamous Cell Carcinoma by Inhibiting miR-200b to Upregulate the IGF2BP2/TK1 Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.680642 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaodan Wu ◽

Yihui Fan ◽

Yupeng Liu ◽

Biao Shen ◽

Haimin Lu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Non Coding Rna

Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.

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lncRNA LINC01296 Promotes Oral Squamous Cell Carcinoma Development by Binding with SRSF1

BioMed Research International ◽

10.1155/2021/6661520 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yanhui Zhang ◽

Aifang Wang ◽

Xiaohe Zhang ◽

Xiaoliang Wang ◽

Jin Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cervical Lymph Node Metastasis ◽

Migration And Invasion ◽

Clinical Samples

Objective. Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, with strong local invasiveness and cervical lymph node metastasis. The purpose of this study was to investigate the role of LINC01296 in oral squamous cell carcinoma and its possible mechanism. Materials and Methods. GEPAI database analysis and clinical samples were used to detect the expression of LINC01296 in head and neck cancer. In vivo experiment, MTT, clone formation assay, and transwell were used to detect the proliferation, migration, and invasion of oral squamous cell carcinoma. The effect of LINC01296 on EMT was detected by western blot and qRT-PCR to measure the expression of epithelial and mesenchymal phenotypic markers. BALB/c nude mice were used to carry out in vitro treatment experiment. In terms of mechanism, the binding relationship between LINC01296 and SRSF1 was predicted and verified by the RBPDB database and RNA pull-down assay. Results. LINC01296 was highly expressed in clinical samples and cell lines of oral squamous cell carcinoma. Overexpression of LINC01296 promoted the proliferation, invasion, and migration of oral squamous cell carcinoma cells and accelerated the formation of xenografts, while silencing LINC01296 inhibited tumor progression. In mechanism, LINC01296 plays a tumor-promoting role by binding to SRSF1 protein. Conclusion. LINC01296 promotes malignant lesions in oral squamous cell carcinoma by binding to SRSF1 protein, which provides important experimental data and theoretical basis for the prevention, diagnosis, and treatment of oral squamous cell carcinoma.

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LncRNA MCM3AP-AS1 promotes proliferation, migration and invasion of oral squamous cell carcinoma cells via regulating miR-204-5p/FOXC1

Journal of Investigative Medicine ◽

10.1136/jim-2020-001415 ◽

2020 ◽

Vol 68 (7) ◽

pp. 1282-1288

Author(s):

Hui Li ◽

Junhong Jiang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Qrt Pcr ◽

Gene Assay

Oral squamous cell carcinoma (OSCC) is a lethal malignancy. It is reportedly demonstrated that long non-coding RNA (lncRNA) participates in the development of OSCC. The purpose of this study was to clarify the function and possible molecular mechanisms of lncRNA MCM3AP antisense RNA 1 (lncRNA MCM3AP-AS1) in OSCC. Quantitative real-time PCR (qRT-PCR) was adopted to investigate MCM3AP-AS1 expressions in OSCC tissues and cells. The proliferation, migration and invasion of HN-6 and SCC-9 cells were probed by cell counting kit-8 and Transwell assays, respectively. Dual luciferase reporter gene assay, Pearson’s correlation analysis, qRT-PCR and western blot were used to detect the binding relationship among miR-204-5 p, MCM3AP-AS1 and forkheadbox C1 (FOXC1). MCM3AP-AS1 expression was elevated in OSCC tissues and cell lines. Overexpression of MCM3AP-AS1 facilitated the proliferation, migration and invasion of OSCC cells, while the knockdown of MCM3AP-AS1 suppressed these malignant phenotypes. Besides, MCM3AP-AS1 impeded miR-204-5 p by binding with it. MCM3AP-AS1 could also upregulate the expression of FOXC1 via repressing miR-204-5 p.MCM3AP-AS1 promotes the progression of OSCC cells by adsorbing miR-204-5 p and upregulating FOXC1 expressions.

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MicroRNA-99a-5p suppresses cell proliferation, migration, and invasion by targeting isoprenylcysteine carboxylmethyltransferase in oral squamous cell carcinoma

Journal of International Medical Research ◽

10.1177/0300060520939031 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052093903

Author(s):

Xiang Sun ◽

Huixin Yan

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Squamous Cell ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Isoprenylcysteine Carboxylmethyltransferase

Background MicroRNA (miR)-99a-5p acts as a tumor suppressor in several tumors, including bladder cancer and breast cancer, but its biological function in oral squamous cell carcinoma (OSCC) is poorly understood. Methods miR-99a-5p expression was determined in OSCC tissues and cell lines using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by the Cell Counting Kit-8 assay and colony formation assay. Wound healing and Transwell assays were used to analyze migration and invasion abilities, respectively, in OSCC cells. The luciferase reporter assay, RT-qPCR, and western blotting were used to determine the relationship between miR-99a-5p and isoprenylcysteine carboxylmethyltransferase (ICMT). Results miR-99a-5p expression in OSCC tissues and cell lines was significantly decreased compared with corresponding controls, and was significantly associated with clinical stage and lymph node metastasis in OSCC. Functional assays revealed that miR-99a-5p overexpression significantly inhibited the proliferation, migration, and invasion abilities of CAL-27 and TCA-8113 OSCC cells. miR-99a-5p was found to directly target ICMT, while ICMT restoration reversed the role of miR-99a-5p in OSCC cells. Conclusions Our results indicate that miR-99a-5p-mediates the down-regulation of ICMT, which could be used as a novel potential therapeutic target for OSCC treatment.

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CircZNF236 Facilitates Malignant Progression in Oral Squamous Cell Carcinoma by Sequestering miR-145-5p

10.21203/rs.3.rs-805500/v1 ◽

2021 ◽

Author(s):

Qing Lu ◽

Yanhai Che ◽

Hongze Che ◽

Min Hu

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Xenograft Model ◽

Tumor Formation ◽

Cell Counting ◽

Luciferase Reporter ◽

Circular Rnas

Abstract BackgroundA number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC).MethodsWe first examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and flow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumour domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. ResultsOSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF2361 levels in patients with OSCC correlated with a poor prognosis. CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression.ConclusionCircZNF236 modulates OSCC via an miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.

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miRNA-101 Targets TGF-βR1 to Retard the Progression of Oral Squamous Cell Carcinoma

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504019x15761480623959 ◽

2020 ◽

Vol 28 (2) ◽

pp. 203-212 ◽

Cited By ~ 1

Author(s):

Yong Wang ◽

Rui-Zhi Jia ◽

Shu Diao ◽

Jun He ◽

Li Jia

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Transforming Growth Factor ◽

Ectopic Expression ◽

Transforming Growth Factor Β ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion

Despite the considerable knowledge on the involvement of microRNA-101 (miR-101) in the evolution of oral squamous cell carcinoma (OSCC), the underlying mechanisms remain obscure. In this study, miR-101 expression was markedly downregulated in the OSCC cell lines and tissues. Cell counting kit-8 (CCK-8), ethynyl deoxyuridine (EdU), and colony formation assays showed that miR-101 inhibited the proliferation of OSCC cells. Flow cytometry and caspase 3 activity assays indicated that miR-101 induced OSCC cell apoptosis. Transwell assays demonstrated that this miRNA also repressed OSCC cell migration and invasion. Moreover, tube formation assay showed that miR-101 abated the proangiogenesis of OSCC cells. Dual-luciferase reporter assay confirmed that miR-101 directly targeted transforming growth factor-β receptor 1 (TGF-βR1) in OSCC. Ectopic expression of TGF-βR1 counteracted the effects of miR-101 on the OSCC cell characteristics. Thus, miR-101 significantly abolished the proliferation, motility, and proangiogenesis of OSCC cells and induced their apoptosis by targeting TGF-βR1. These results imply the potential application of miR-101 in OSCC treatment.

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Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis

10.21203/rs.2.12980/v5 ◽

2020 ◽

Author(s):

Deyu Liu ◽

Xinchun Jian ◽

Pu Xu ◽

Rong Zhu ◽

Yuan Wang

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Clinical Importance ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Repressive Effect

Abstract Background: Increasing studies have demonstrated that long non-coding RNAs (lncRNAs) play an important role in tumor progression. However, the potential biological functions and clinical importance of Linc01234 in oral squamous cell carcinoma (OSCC) remain unclear. Methods: We evaluated the expression profile and prognostic value of Linc01234 in OSCC tissues by RT-qPCR. Then, functional in vitro experiments were performed to investigate the effects of Linc01234 on tumor growth, migration and invasion in OSCC. Mechanistically, RT-qPCR, bioinformatic analysis and dual luciferase reporter assays were performed to identify a competitive endogenous RNA (ceRNA) mechanism involving Linc01234, miR-433-3p and PAK4. Results: We found that Linc01234 was clearly upregulated in OSCC tissues and cell lines, and its level was positively associated with T stage, lymph node metastasis, differentiation and poor prognosis of patients with OSCC. Our results shown that Linc01234 inhibited cell proliferation and metastatic abilities in CAL27 and SCC25 cells following its knockdown. Mechanistic analysis indicated that Linc01234 may act as a ceRNA (competing endogenous RNA) of miR-433-3p to relieve the repressive effect of miR-433-3p on its target PAK4. Conclusions: Our results indicated that Linc01234 promotes OSCC progression through the Linc01234/miR-433/PAK4 axis and might be a potential therapeutic target for OSCC.

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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.

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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.

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Knockdown of circ_0011946 targets miR-216a-5p/BCL2L2 axis to regulate proliferation, migration, invasion and apoptosis of oral squamous cell carcinoma cells

BMC Cancer ◽

10.1186/s12885-021-08779-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Zhou ◽

Shuhong Zhang ◽

Zhonghan Min ◽

Zhongwei Yu ◽

Huaiwei Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

B Cell Lymphoma ◽

Luciferase Reporter ◽

Migration And Invasion

Abstract Background Circular RNAs (circRNAs) are implicated in the development of oral squamous cell carcinoma (OSCC). The aim of current research is to elucidate the role and mechanism of circ_0011946 in the functional behaviors of OSCC cells. Methods Circ_0011946, microRNA (miR)-216a-5p, B cell lymphoma-2-like 2 protein (BCL2L2) abundances were exposed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation, migration, invasion and apoptosis were detected by MTT, colony formation assay, transwell, wound-healing and flow cytometry assays, respectively. Target correlation was tested by dual-luciferase reporter and RNA pull-down assays. An in vivo xenograft experiment was employed to investigate the function of circ_0011946 on tumor growth in vivo. Results Circ_0011946 and BCL2L2 levels were increased, while miR-216a-5p level was decreased in OSCC tissues and cells. Circ_0011946 knockdown impeded proliferation, migration, and invasion, but promoted apoptosis in OSCC cells. Circ_0011946 functioned as a sponge for miR-216a-5p, and BCL2L2 was targeted by miR-216a-5p. Besides, miR-216a-5p or BCL2L2 knockdown partly attenuated the inhibitory influences of circ_0011946 silence or miR-216a-5p overexpression on OSCC cell progression. Furthermore, circ_0011946 post-transcriptionally regulated BCL2L2 through sponging miR-216a-5p. Moreover, circ_0011946 knockdown constrained OSCC tumor growth in vivo. Conclusion Circ_0011946 silence repressed OSCC cell proliferation, migration, and invasion, but promoted apoptosis through the regulation of the miR-216a-5p/BCL2L2 axis.

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