Long noncoding RNA TPT1-AS1 promotes the progression and metastasis of colorectal cancer by upregulating the TPT1-mediated FAK and JAK-STAT3 signalling pathways
发布时间 :2021-09-01
研究对象: TPT1; colorectal cancer; long noncoding RNA; metastasis; tumour protein translationally controlled 1 antisense RNA 1; 期刊: Aging (Albany NY); 影响因子 :5.682; 合作单位:中南大学湘雅第二医院; 发表时间:2021年1月


Tumour protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1-AS1) is known to be involved in the development and metastasis of cervical and ovarian cancers; however, its biological role in colorectal cancer (CRC) remains unknown. This study aimed to determine the function and mechanism of action of TPT1-AS1 in the progression and metastasis of CRC. Elevated TPT1-AS1 levels were observed in CRC tissues. Furthermore, the high expression levels were found to be correlated with unfavourable clinicopathological characteristics in CRC. Cell function experiments demonstrated that TPT1-AS1 depletion impeded cell proliferation, migration and invasion and enhanced cell adhesion; it also attenuated tumorigenesis and metastasis in vivo. Additionally, TPT1-AS1 was predominately located in the nuclei of the cells and could upregulate the expression of TPT1 by recruiting mixed lineage leukaemia protein-1 (MLL1), which increased the trimethylation of H3K4 me3 in the TPT1 promoter region and subsequently activated FAK and JAK-STAT3 signalling cascades. The inhibition of FAK activation by PF573228 significantly attenuated the oncogenic effect of TPT1-AS1. These findings indicated that TPT1-AS1 promoted tumour progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signalling pathways. Thus, TPT1-AS1 may be considered as a potential therapeutic target for CRC.


合作技术:FISH 探针