Tissue Eng Regen Med.  2024 Jun;21(4):595-608. 10.1007/s13770-024-00625-5.

Signal Transducer and Activator of Transcription 4-Induced UpRegulated LINC01278 Enhances Proliferation and Invasion of Non-Small Cell Lung Cancer Cells via the MicroRNA-877-5p/ Activating Transcription Factor 4 Axis

• Yang L
• Xiao Y
• Deng S
• Yan D
• Li Z
• Wang Y
• Lei C

• KMID: 2556268
• DOI: http://doi.org/10.1007/s13770-024-00625-5

Abstract

BACKGROUND
The purpose of this study was to investigate the specific effects of signal transducer and activator of transcription 4 (STAT4)-induced long intergenic nonprotein coding RNA 1278 (LINC01278) on the growth of non-small cell lung cancer (NSCLC) cells involved in the microRNA (miR)-877-5p/activated transcription factor 4 (ATF4) axis.
METHODS
NSCLC tumor tissue and adjacent normal tissue were collected. Human normal lung epithelial cell BEAS-2B and human NSCLC cell lines (H1299, H1975, A549, H2228) were collected. The expression levels of STAT4, LINC01278, miR-877-5p, and ATF4 were detected. A549 cells were screened for subsequent experiments. The proliferation ability of cells was detected by colony formation experiment. Cell apoptosis was tested by flow cytometry. Scratch test and transwell assay were used to detect the migration and invasion ability of cells. Biological function of LINC01278 in NSCLC was confirmed by xenograft experiments.
RESULTS
Low expression miR-877-5p and high expression of STAT4, LINC01278 and ATF4 were detected in NSCLC. Silenced LINC01278 in A549 cell depressed cell proliferation, migration and invasion, but facilitated cell apoptosis. LINC01278 was positively correlated with STAT4 and could directly bind to miR-877-5p. Upregulating miR-877-5p suppressed NSCLC cell progression, while downregulating miR-877-5p had the opposite effect. Upregulating miR-877-5p abrogated the effects of silenced LINC01278 on NSCLC cell progression. MiR-877-5p targeted ATF4. ATF4 upregulation could partly restore the carcinogenic effect of LINC01278 in vitro and in vivo.
CONCLUSION
Our data supports that STAT4-induced upregulation of LINC01278 promotes NSCLC progression by modulating the miR-877-5p/ATF4 axis, suggesting a novel direction for NSCLC treatment.

Keyword

Non-small cell lung cancer; LINC01278; MicroRNA-877-5p; Activating transcription factor 4