RESUMO
OBJECTIVES: To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. BACKGROUND: MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. METHODS: The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.
Assuntos
Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Circular , Proteínas de Ligação a RNA , Humanos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , RNA Circular/genética , Regulação Neoplásica da Expressão Gênica , Masculino , Proliferação de Células/genética , Linhagem Celular Tumoral , Feminino , Camundongos , Animais , Movimento Celular/genética , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
INTRODUCTION: MicroRNAs (miRNAs) play important roles in tumorigenesis. In this study, we investigated the role of miR-221 in the development and progression of clear cell renal cell carcinoma (ccRCC). METHODS: Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of miR-221 in ccRCC tissues and cell lines. Then, we investigated the role of miR-221 to determine its potential roles on renal cancer cell proliferation, migration and invasion in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-221 and the results were validated in renal cancer cells. RESULTS: In the present study, we found that miR-221 was significantly increased in ccRCC tissues and cell lines. Knocked-down expression of miR-221 remarkably inhibited cell proliferation, migration and invasion of renal cancer cells. Moreover, at the molecular level, our results suggested that TIMP2 as a direct target of miR-221 through which miR-221 promoted tumor cell proliferation, migration and invasion. CONCLUSIONS: These findings suggested that miR-221 play an oncogenic role in the renal cancer cell proliferation, migration and invasion by directly inhibiting the tumor suppressor TIMP2, indicating miR-221 act as a potential new therapeutic target for the treatment of ccRCC.
Assuntos
Carcinoma de Células Renais/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Renais/metabolismo , MicroRNAs/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Regiões 3' não Traduzidas , Sítios de Ligação , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Genes Reporter , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/genética , Invasividade Neoplásica , Oncogenes , Interferência de RNA , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-2/genética , TransfecçãoRESUMO
This study was aimed to explore the expression of CD34 in patients with biphenotypic acute leukemia (BAL) and its relation with the prognosis of BAL. The flow cytometry was used to detect leukemia-associated antigen. The used monoclonal antibodys (McAb) included CD10, CD19 and CD34 for B lymphocyte lineage, CD2, CD3 and CD5 for T lymohocyte lineage, MPO, CD13 and CD33 for myeloid lineage. The finally results were respectively analyzed. The results indicated that 9 out of 216 cases of leukemia was diagnosed as BAL (4.2%). Among 9 cases of BAL, 6 cases showed the common expression of myeloid and T lymohocyte lineages (66.7%), 3 cases showed the common expression of myeloid and B lymohocyte lineages (33.3%). 4 cases of BAL displayed CD34 positive expression (44.4%). As compared with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), the BAL patients showed higher CD34 positive expression (P < 0.05). It is concluded that the BAL patients show a poor prognosis, as compared with AML or ALL patients. The therapeutic effect of BAL may negatively correlate with the CD34 positive expression.