Abstract
BackgroundsA number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We aimed to investigate the effect and mechanisms of circ-FBXW7 on CRC progression.MethodsThe expression of circ-FBXW7 in CRC patients was detected by PCR. Stably knockdown of circ-FBXW7 (si circ-FBXW7) cell lines and overexpression of circ-FBXW7 (oe circ-FBXW7) cell lines were constructed by small interfering RNA method and plasmids transfection in CRC SW480 and SW620 cells. The functional experiments including cell proliferation, migration and invasion were carried out by cell counting kit-8 (CCK-8) assay, wound healing assay and trans well assay. The xenograft animal models were established to evaluate the effect and the underlying molecular mechanisms of circ-FBXW7 on CRC progression.ResultsCRC samples had a significantly lower level of circ-FBXW7 compared to normal tissue. si circ-FBXW7 notably promoted the proliferation, colony formation, cell migration and invasion of CRC cell in vitro. On contrast, circ-FBXW7 overexpressed significantly suppressed CRC cell proliferation, migration and invasion. Similarly, si circ-FBXW7 stimulated the tumor growth and circ-FBXW7 overexpression repressed the tumor progression in SW480 and SW620 tumor models, which suggested that circ-FBXW7 could serve as a target biomarker of CRC. Further study found that si circ-FBXW7 up-regulated the mRNA and protein expressions of NEK2 and mTOR, and diminished the PTEN expression. Whereas, overexpressed circ-FBXW7 induced the tumor suppression via reversing the expressions of NEK2, mTOR, and PTEN.Conclusioncirc-FBXW7 plays a major role in controlling the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and may be a potential therapeutic target for CRC treatment.Graphical abstractCirc-FBXW7 controls the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and its overexpression inhibits colorectal cancer cell migration and invasion, suggesting the potential therapeutic target for CRC treatment.
Highlights
Colorectal cancer (CRC) is the fourth diagnosed cancer and the second leading cause of cancer-related death with increasing morbidity in the population [1]
The expression of circ-F-box and WD repeat domain containing 7 (FBXW7) in clinical CRC patients The expression of circ-FBXW7 was detected in ten pairs of cancerous and adjacent noncancerous tissues derived from CRC patients
Circ-FBXW7 inhibited the CRC cell proliferation The knockdown and overexpression of circ-FBXW7 were established in SW480 and SW620 cancer cell lines
Summary
Colorectal cancer (CRC) is the fourth diagnosed cancer and the second leading cause of cancer-related death with increasing morbidity in the population [1]. Despite recent improvements in early diagnosis and the development of more effective treatments for CRC, some of CRC patients are failed to respond to the treatments. The newest targeted therapeutic drugs do not cure the patient or induced the drug resistance [2]. It is critical for improving understanding of the underlying cellular basis of CRC to the development of novel therapeutics drugs. Numerous factors including gene mutation, aberrant DNA methylation, microRNA (miRNA) [3], noncoding RNA deregulation, and circular RNAs (circRNAs) [4] are involved in CRC [5]. Ten circRNAs are involved in the regulation of cell proliferation, migration, and invasion in CRC [6]
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