MicroRNA-760 inhibits cell proliferation and invasion of Colorectal cancer by targeting the SP1-mediated PTEN/AKT signalling pathway

Abstract

Colorectal cancer (CRC), one of the most commonly diagnosed types of cancer worldwide, is the third most prevalent and fourth most frequent cause of cancer-related mortality. Dysregulated microRNAs (miRNAs) have potential regulatory roles in the development and progression of various cancer types. Therefore, the investigation of the miRNAs involved in CRC formation and progression may lead to the development of highly effective therapeutic strategies for CRC. In the present study, miRNA-760 (miR-760) was frequently downregulated in CRC tissues and cell lines. The low levels of miR-760 expression were significantly correlated with the tumor size, lymph node metastasis and TNM stage of CRC. Functional assays revealed that restoring miR-760 expression inhibited CRC cell proliferation and invasion in vitro. The results of bioinformatics analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis suggested that specificity protein 1 (SP1) is a direct target of miR-760 in CRC. The high expression of SP1 in CRC tissues was inversely correlated with the expression of miR-760. Rescue experiments demonstrated that enforced SP1 expression rescued the tumor-suppressing effects of miR-760 on CRC cell proliferation and invasion. In addition, miR-760 overexpression is involved in the regulation of the PTEN/AKT signalling pathway. Collectively, the present data demonstrated that miR-760 directly targets SP1 to inactivate the PTEN/AKT signalling pathway, thus implicating miR-760 in the regulation of CRC cell proliferation and invasion. Therefore, miR-760 may be a novel biomarker and therapeutic target for CRC.