RESUMO
Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour-promoting effects of circCSNK1G3 were, at least partly, achieved by up-regulating miR-181b. Increased miR-181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR-181b expression, which leads to TIMP3-mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circCSNK1G3 in cancer research deserve further investigation.
Assuntos
Carcinoma de Células Renais , Caseína Quinase I/genética , Neoplasias Renais , MicroRNAs , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Proteínas Supressoras de Tumor/genéticaRESUMO
Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.
Assuntos
Biomarcadores Tumorais/genética , Vesículas Extracelulares/genética , MicroRNAs/genética , Neoplasias/patologia , RNA Mensageiro/genética , RNA não Traduzido/genética , Microambiente Tumoral/imunologia , Animais , Progressão da Doença , Humanos , Metástase Neoplásica , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismoRESUMO
miRNAs are a class of single-stranded noncoding RNAs, which have no coding potential, but modulate many molecular mechanisms including cancer pathogenesis. miRNAs participate in cell proliferation, differentiation, apoptosis, as well as carcinogenesis or cancer progression, and their involvement in lung cancer has been recently shown. They are suggested to have bidirectional functions on important cancer-related genes so as to enhance or attenuate tumor genesis. Epithelial-mesenchymal transition (EMT) is a fundamental process which contributes to integrity of organogenesis and tissue differentiation as well as tissue repair, organ fibrosis and the progression of carcinoma, and several miRNAs were suggested to form the network regulating EMT in lung cancer, among which, miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) play crucial roles in the suppression of EMT.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Progressão da Doença , Epigênese Genética , Genes Supressores de Tumor , Humanos , Neoplasias Pulmonares/patologia , MicroRNAs/genéticaRESUMO
Lung cancer, the leading cause of cancer deaths worldwide, is characterized with malignantâ¯cell growth. Advances in next-generation sequencing has helped us further understand RNA and identify novel circular RNAs (circRNAs) that may be useful in the early diagnosis and treatment of lung cancer. Similar to other noncoding RNAs, circRNAs present diverse biological functions in normal and disease states, including various types of cancers. This review focuses mainly on the poorly understood functions of circRNA in lung cancer. This paper also summarizes the recent advances in circRNA biogenesis, analyzes the role of circRNAs in cancers, and discusses the potential mechanisms of circRNAs in lung cancer.