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Long Non-coding RNA TPT1-AS1 Suppresses APC Transcription in a STAT1-Dependent Manner to Increase the Stemness of Colorectal Cancer Stem Cells


Cancer stem cells (CSCs) are the major culprits leading to a new level of complexity and the consequential therapy resistance and disease recurrence in colorectal cancer (CRC). This study focuses on the effect of long non-coding RNA (lncRNA) TPT1-AS1 and its associated molecules on the stemness maintenance of CRC stem cells. TPT1-AS1 was identified as a significantly upregulated gene in CRC using the GSE146587 dataset. Stem cells from CRC HCT116 and CACO2 cells were isolated. TPT1-AS1 was significantly highly expressed in the CSCs compared to non-stem cells. Downregulation of TPT1-AS1 reduced the stemness of the CRC stem cells. TPT1-AS1 recruited STAT1 to the promoter region of APC to suppress APC transcription. Further upregulation of STAT1 or downregulation of APC blocked the role of TPT1-AS1 silencing and restored the malignant behaviors of CSC stem cells. APC inactivated the Wnt/β-catenin pathway. Overexpression of STAT1 restored the levels of cyclin D1 and β-catenin in cells suppressed by TPT1-AS1 silencing. In summary, this work demonstrates that TPT1-AS1 recruits STAT1 to suppress APC transcription and increase the stemness of colorectal CSCs via Wnt/β-catenin activation.

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Data Availability

The analyzed datasets generated during the study are available from the corresponding author on reasonable request.



Analysis of variance


Adenomatous polyposis coli


Chromatin immunoprecipitation


Cancer stem cells


Dulbecco's modified Eagle medium


Fetal bovine serum


Fluorescence in situ hybridization


Glyceraldehyde-3-phosphate dehydrogenase


Gene expression omnibus


Hematoxylin–eosin staining


Horseradish peroxidase


Immunoglobulin G

Mean ± SD:

Mean ± standard deviation




Phosphate-buffered saline




RNA immunoprecipitation


Signal transducer and activator of transcription 1


The cancer genome atlas




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This work was supported by the Project of Changzhou Medical Innovation Team (CCX201807).

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Authors and Affiliations



BXC is the guarantor of integrity of the entire study and contributed to the concepts; BXC, HJS, STX, and QM contributed to the data acquisition and statistical analysis; BXC contributed to the experimental studies; BXC and HJS contributed to the manuscript preparation. All authors read and approved the final manuscript.

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Correspondence to Qi Mo.

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The authors declare that they have no conflict of interest.

Ethical Approval

All animal experiments were approved by the Animal Ethical Committee of Changzhou No. 2 People’s Hospital and strictly performed in accordance with the National Institutes of Health Guide to the Care and Use of Laboratory Animals (8th edition, 2011).

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Chen, B., Sun, H., Xu, S. et al. Long Non-coding RNA TPT1-AS1 Suppresses APC Transcription in a STAT1-Dependent Manner to Increase the Stemness of Colorectal Cancer Stem Cells. Mol Biotechnol 64, 560–574 (2022).

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  • Long non-coding RNA TPT1-AS1
  • Colorectal cancer
  • CSCs
  • STAT1
  • APC