RESUMO
Colorectal cancer (CRC) features high prevalence and mortality. Long non-coding RNAs (lncRNAs) exert nonnegligible roles in human cancer development. Nevertheless, the functions of most lncRNAs still remain unexplored. We currently focused on detecting the influence of SPINT1 antisense RNA 1 (SPINT1-AS1) on CRC development and investigating into the potential regulatory mechanism. RT-qPCR analysis first confirmed that SPINT1-AS1 exhibited high expression in KRAS-mutant (KRASMUT) CRC cells. Through series of functional experiments, we observed that knockdown of SPINT1-AS1 weakened KRASMUT CRC cell proliferation, migration and invasion. Afterwards, the implementation of mechanism assays help to verify that SPINT1-AS1 sequestered microRNA-433-3p (miR-433-3p) to regulate the expression of E2F transcription factor 3 (E2F3). Besides, E2F3 was validated to activate the transcription of SPINT1-AS1 in turn. Rescue experiments confirmed the functional influence of SPINT1-AS1/miR-433-3p/E2F3 on CRC cells. In summary, the molecular axis of SPINT1-AS1/miR-433-3p/E2F3 forms a positive loop which might become a potential biomarker in CRC.
Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Retroalimentação , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Secretadas Inibidoras de Proteinases/genética , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Fator de Transcrição E2F3RESUMO
Lung adenocarcinoma (LUAD) is difficult to cureradically. Long non-coding RNAs (lncRNAs) in LUAD are a hotspot in molecular research, however, the role of lncRNA ASMTL-AS1 in LUAD is still unknown. Our study explores the role and mechanisms of ASMTL-AS1 in LUAD. Quantitative reverse transcription PCR or western blot was utilized to analyze the expression of RNAs or proteins. The influences of ASMTL-AS1 and SAT1 on LUAD cells were analyzed by functional assays. Biological instruments were applied to observe ferroptosis-related markers. In vivo assays were performed to uncover the impact of ASMTL-AS1 on LUAD. Moreover, mechanism assays were done to confirm the relationship among ASMTL-AS1, SAT1 and U2AF2. Results showed that ASMTL-AS1 was down-regulated in LUAD cells and ASMTL-AS1 up-regulation resulted in retarded LUAD cell and xenograft tumor growth along with stimulated ferroptosis. ASMTL-AS1 recruited U2AF2 to stabilize SAT1 mRNA. Furthermore, SAT1 exerted a cancer suppressor role in LUAD cells. In conclusion, we first demonstrated that ASMTL-AS1 positively regulated SAT1 to promote ferroptosis and could stabilize SAT1 mRNA via recruiting U2AF2, shedding a light on a novel molecular mechanism in LUAD progression.
Assuntos
Acetiltransferases/metabolismo , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Ferroptose , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metiltransferases/metabolismo , Biomarcadores/metabolismo , Western Blotting , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
Forkhead box protein M1 (FOXM1), an important regulator of tumorigenesis in various human tumors, has recently been reported to play a role in the modulation of radiosensitivity in glioma and breast cancer cells. The present study aimed to investigate the effects of FOXM1 on radiotherapy resistance in human lung cancer and to explore the related molecular mechanisms. The results revealed that FOXM1 expression was upregulated in A549 and H1299 cells after IR (Ionizing radiation). FOXM1 inhibition impeded survival fractions, impeded proliferation, and triggered apoptosis after IR. Moreover, the silencing of FOXM1 dampened cell migration, invasion, and EMT (epithelial-mesenchyman transition) in A549 and H1299 cells treated by IR. In addition, KIF20A was also highly expressed in IR-treated A549 cells and downregulated by FOXM1 inhibition. Knockdown of KIF20A inhibited the survival fraction. Reintroduction of KIF20A partly reversed the effects of FOXM1 on the proliferation, apoptosis, and metastasis of A549 cells. Taken together, these results indicated that FOXM1 might enhance radioresistance partly through the induction of KIF20A expression.