4.6 Article

Long noncoding RNA TPT1-AS1 promotes the progression and metastasis of colorectal cancer by upregulating the MU-mediated FAK and JAK-STA13 signaling pathways

Journal

AGING-US
Volume 13, Issue 3, Pages 3779-3797

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.202339

Keywords

colorectal cancer; long noncoding RNA; tumour protein translationally controlled 1 antisense RNA 1; TPT1; metastasis

Funding

  1. Natural Science Foundation of China Hunan Science and Technology Department [2019JJ40429]
  2. key research and development projects of Hunan Science and Technology Department [2016JC2048]
  3. major special projects of Hunan Science and Technology Department [2017SK103]

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TPT1-AS1 promotes tumor progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signaling pathways.
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.

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