RESUMO
Cholangiocarcinoma (CHOL) is often diagnosed at an advanced stage; therefore, exploring its key regulatory factors is important for earlier diagnosis and treatment. This study aimed to identify the mechanisms of long non-coding RNA (lncRNA) TMPO Antisense RNA 1 (TMPO-AS1), microRNA let-7 g-5p, and high-mobility group A1 (HMGA1) proteins in CHOL. Our results, through quantitative real-time PCR and Western blot detection, showed that TMPO-AS1 and HMGA1 were overexpressed while let-7 g-5p was underexpressed in CHOL. Cell function experiments in CHOL cells revealed that TMPO-AS1 knockdown inhibited cell proliferation, colony formation, and cell migration, but induced apoptosis. TMPO-AS1 knockdown also suppressed tumor growth in vivo. Together with luciferase assay and Western blotting, we found that TMPO-AS1 could sponge let-7 g-5p to promote HMGA1 expression. Moreover, HMGA1 overexpression attenuated the effect of TMPO-AS1 downregulation in CHOL cells. Overall, our findings identified the oncogenic effect of TMPO-AS1 on CHOL cells, which may put forward a novel methodology for CHOL diagnosis and therapy.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Proteína HMGA1a/genética , MicroRNAs/genética , Proteínas Nucleares/genética , Timopoietinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Colangiocarcinoma/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares/antagonistas & inibidores , RNA Antissenso/fisiologia , RNA Longo não Codificante/fisiologia , Timopoietinas/antagonistas & inibidoresRESUMO
Osteosarcoma (OS) is a common kind of aggressive tumor in bone which was mostly identified in children and adolescents with extremely high risk of death. Accumulating research works have displayed that long noncoding RNAs (lncRNAs) exert an essential role in the development of multiple cancers. It has been reported that TMPO-AS1 is an oncogene in cancers; nonetheless, its molecular mechanism in OS is totally unclear. Our present study elucidated that a remarkable overexpression of TMPO-AS1 was found in OS tissues and cells. Moreover, TMPO-AS1 depletion restrained Wnt/ß-catenin pathway and cell proliferation as well as facilitated cell apoptosis. Further molecular mechanism investigations showed that TMPO-AS1 can sponge to miR-199a-5p. Moreover, miR-199a-5p was at a low level at OS cells. Importantly, miR-199a-5p's overexpression was associated with the OS cells' decreased proliferation and increased apoptosis. In addition, WNT7B was confirmed as a downstream gene of miR-199a-5p. Also the WNT7B expression was reversely modulated by miR-199a-5p and positively modulated by TMPO-AS1. Rescue experiments suggested that downregulated WNT7B rescued miR-199a-5p inhibitor-mediated repression on OS progression, but the treatment of LiCl counteracted the effect of WNT7B downregulation. In a word, TMPO-AS1 serves as a competing endogenous RNA to boost osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis, which provided an underlying therapeutic target for patients with OS.
Assuntos
Biomarcadores Tumorais/metabolismo , MicroRNAs/genética , Proteínas Nucleares/antagonistas & inibidores , Osteossarcoma/patologia , RNA Antissenso/genética , RNA Longo não Codificante/genética , Timopoietinas/antagonistas & inibidores , Proteínas Wnt/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Nucleares/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Timopoietinas/genética , Células Tumorais Cultivadas , Proteínas Wnt/genéticaRESUMO
PURPOSE: Long noncoding RNA (lncRNA) has been identified as an important modulator of gene expression and other activities of the cells. This kind of genes also has a significant role in the growth and development of human cancers, including colorectal cancer (CRC). Among lncRNAs, thymopoietin (TMPO)-antisense RNA 1 (TMPO-AS1) is of particular significance and might have a role in CRC regulation. The current study aimed to determine the involvement of TMPO-AS1 in CRC patients. METHODS: In this study, 50 pairs of tumor and tumor marginal samples of CRC patients were investigated to assess the expression level of TMPO-AS1 in this cancer. For this purpose, the total RNA was isolated from the tissues using the TRIzol RNA extraction method, and after synthesis of the complementary DNA, the TMPO-AS1 expression was measured by quantitative real-time PCR (qRT-PCR) technique. In addition, clinicopathological characteristics of the CRC patients were analyzed in the study groups. RESULTS: The findings demonstrated the overexpression of TMPO-AS1 in CRC tissues. Interestingly, the expression level of TMPO-AS1 was significantly correlated with clinicopathological features of the patients such as lymph node and distant metastasis. CONCLUSION: The overexpression of TMPO-AS1 gene in CRC suggests that this lncRNA and its underlying signaling pathways can be considered a prognostic tumor marker and may pave the way for the future development of novel therapeutic options for CRC.