A novel long non‑coding RNA TTN‑AS1/microRNA‑589‑5p/FOXP1 positive feedback loop increases the proliferation, migration and invasion of pancreatic cancer cell lines

Zhao,Jing; Wu,Fang; Yang,Jun

doi:10.3892/ol.2021.13055

A novel long non‑coding RNA TTN‑AS1/microRNA‑589‑5p/FOXP1 positive feedback loop increases the proliferation, migration and invasion of pancreatic cancer cell lines

Authors:
- Jing Zhao
- Fang Wu
- Jun Yang
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Affiliations: Department of Gastroenterology, Liyang People's Hospital, Liyang, Jiangsu 213300, P.R. China, Department of Gastroenterology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
Published online on: September 17, 2021 https://doi.org/10.3892/ol.2021.13055
Article Number: 794
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous reports have found that long non‑coding (lnc) RNAs were associated with pancreatic cancer (PC) initiation and development. The lncRNA titin antisense RNA 1 (TTN‑AS1) was identified as a tumor promoter in certain types of cancer; however, its role and mechanism in PC remain unclear. The aim of the present study was to investigate the role of TTN‑AS1 in PC and elucidate the underlying mechanism. Reverse transcription‑quantitative PCR analysis was performed to examine the mRNA expression level of TTN‑AS1, microRNA(miR)‑589‑5p and forkhead box protein 1 (FOXP1). Knockdown experiments were performed to examine the effect of TTN‑AS1 on PC cell proliferation, migration and invasion. Luciferase reporter assays validated the binding of miR‑589‑5p to TTN‑AS1 and FOXP1. Chromatin immunoprecipitation and luciferase reporter assays confirmed the binding ability of FOXP1 to the TTN‑AS1 promoter. As a result, TTN‑AS1 and FOXP1 were found to be upregulated in PC cell lines and tissues, while miR‑589‑5p was expressed at low levels. Knockdown experiments indicated the suppressive effect of TTN‑AS1 knockdown on cell proliferation, migration and invasion in PC cell lines. Further mechanistic research uncovered that TTN‑AS1 functioned as a molecular sponge for miR‑589‑5p and its mRNA expression level in PC tissues was inversely associated with that of miR‑589‑5p. Furthermore, miR‑589‑5p was confirmed to target FOXP1. Of note, it was discovered that FOXP1 transcriptionally activated TTN‑AS1 mRNA expression level. Taken together, the findings of the present study demonstrated that the new TTN‑AS1/miR‑589‑5p/FOXP1 feedback loop may play an important role in PC.

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