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1.
Cell Biol Toxicol ; 38(1): 129-146, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33656636

RESUMO

Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Neoplasias da Bexiga Urinária/metabolismo
2.
Exp Cell Res ; 385(1): 111649, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31562861

RESUMO

Exosomes are present within the local hypoxic tumor microenvironment, where they are able to transfer microRNAs between cells, thereby, effectively mediating cell-cell communication. Hypoxia plays a pivotal role in the progression of many tumor types such as hepatocellular carcinoma (HCC), but how hypoxia-induced exosomes in HCC affect HCC cells remains uncertain. In the present study, we found that hypoxic conditions induced increased exosomal production by HCC cells, and these exosomes, in turn, enhanced the proliferation, migration, and invasiveness in addition to epithelial-to-mesenchymal transition (EMT) in HCC cells under normoxic conditions. When we analyzed these exosomes, we found that miR-1273f were present at higher levels under hypoxic conditions, and we determined that this miRNA was responsible for directly replicating the effects of hypoxic exosomes within HCC cells, in addition to activating the Wnt/ß-catenin signaling. We finally identified LHX6, which is a known inhibitor of the Wnt/ß-catenin pathway, to be a miR-1273f target. These results, thus, provide evidence that hypoxic conditions can lead HCC cells to express increased exosomes that facilitate miR-1273f expression in normoxic cells, thereby enhancing their malignant phenotype at least in part by targeting LHX6 for downregulation.


Assuntos
Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Exossomos/genética , Hipóxia/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Metástase Neoplásica/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/patologia , Metástase Neoplásica/patologia , Microambiente Tumoral/genética , Via de Sinalização Wnt/genética
3.
Aging (Albany NY) ; 13(4): 5986-6009, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33612481

RESUMO

BACKGROUND: This study aimed to investigate the aberrant expression of hsa_circ_0002874 in non-small cell lung cancer (NSCLC) and elucidate associated molecular mechanisms that influence apoptosis and induce paclitaxel (PTX) resistance. METHODS: Inhibitors were used to downregulate circRNA or miRNA expression. pCDNA plasmid transfection and mimics were used to upregulate circRNA or miRNA expression. Dual-luciferase reporter assays were conducted to evaluate interactions between miR1273f and MDM2. Xenograft tumor models were used to assess the effect of hsa_circ_0002874 and miR1273f on tumor growth. NSCLC tissues and matched non-cancerous tissues were also collected for correlation analysis. RESULTS: hsa_circ_0002874 acts as a sponge for miR1273f which targets MDM2/P53. The stability of the hsa_circ_0002874/miR1273f/MDM2/P53 pathway was verified by upregulating and downregulating the expression of hsa_circ_0002874 and miR1273f. hsa_circ_0002874 downregulation or miR1273f upregulation reversed the resistance of the A549/Taxol cells in xenograft models. The expression of hsa_circ_0002874 was high, and the level of MDM2 was low in NSCLC tissues. P53 was only weakly expressed in NSCLC tissues with high expression of MDM2. CONCLUSIONS: hsa_circ_0002874 is strongly expressed in NSCLC tissues and maybe a potential marker for PTX resistance. hsa_circ_0002874 downregulation could regulate miR1273f/MDM2/P53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Paclitaxel/farmacologia , Transdução de Sinais , Células A549 , Idoso , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-mdm2/genética , RNA Circular , Proteína Supressora de Tumor p53
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