Abstract
BackgroundMicroRNAs (miRNAs) play an important role in tumor occurrence. The role of miR-378a-5p and CDK1 in colorectal cancer (CRC) was investigated in this study.MethodsInvestigation of TCGA database and the detection of miR-378a-5p expression in colorectal cancer pathological tissues and colorectal cancer cell lines were undertaken by using qRT-PCR. We performed cell function experiments (CCK-8 assay, EdU assay, colony formation assay, wound healing assay, transwell assay, cell apoptosis assessment, and cell cycle assessment) and nude mouse tumor formation experiments to evaluate the effects of miR-378a-5p on proliferation, metastasis, and invasion to explore the role of miR-378a-5p in vivo and in vitro. Next, through TCGA database, immunohistochemical staining of pathological tissues, and cell function experiments, the role of the target gene CDK1 of miR-378a-5p was verified by database prediction, and dual luciferase reporter gene experiments in colorectal cancer cells were performed. Finally, whether upregulation of CDK1 restores the inhibitory effect of overexpression of miR-378a-5p on the proliferation of CRC cells was studied by overexpression of CDK1.ResultsBioinformatic analysis showed significant downregulation of miR-378a-5p levels in colorectal cancer (CRC). Cell function experiments and tumor xenograft mouse models confirmed the low expression of miR-378a-5p within CRC tissues, which indicated the tumor suppressive role of miR-378a-5p in CRC. To better explore the regulation of miR-378a-5p in CRC, we predicted and validated cell cycle-dependent protein kinase 1 (CDK1) as the miR-378a-5p target gene and observed that miR-378a-5p suppressed CRC cell proliferation by targeting CDK1.ConclusionThe results of this study help to elucidate the mechanism by which miR-378a-5p can be used as a tumor marker to inhibit the growth of colorectal cancer and CDK1, which is related to the prognosis of colorectal cancer patients. MiR-378a-5p inhibits CRC cell proliferation by suppressing CDK1 expression, which may become a possible therapeutic target for treatment of CRC.
Highlights
Colorectal cancer (CRC) is a frequently occurring malignant tumor occurring in the digestive system
Results miR-378a-5p is expressed at lower levels in colorectal cancer (CRC) The Cancer Genome Atlas (TCGA) database was used to analyze microRNAs differentially expressed in CRC, and miR-6833, miR-1248, miR-1277, and remarkable upregulation of miR-378a-5p in CRC tissues were observed (Fig. 1a)
We focused on studying the differential expression of miR-378a-5p (Fig. 1b), and the miR-378a-5p levels within the 22 CRC tissue samples together with matched adjacent noncarcinoma tissue samples were assessed through qPCR, which indicated a decreased miR-378a-5p expression within the CRC tissue samples (Fig. 1c)
Summary
Colorectal cancer (CRC) is a frequently occurring malignant tumor occurring in the digestive system. Despite the increasing number of new therapies for CRC, the treatment outcome for patients with advanced CRC is not satisfactory. It is of great significance to develop new treatments. Tumor cells are mainly characterized by uncontrolled growth, disturbed cell cycle, and indefinite proliferation ability, in which disturbance of the cell cycle may lead to tumorigenesis. Cell cycle-dependent protein kinase 1 (CDK1), which belongs to the serine/threonine-protein kinase family, is mainly active in the late G2 and early M phases, and high expression of active CDK1 can promote the G2/M transition and accelerate the growth of tumor cells [6,7,8]. The role of miR-378a-5p and CDK1 in colorectal cancer (CRC) was investigated in this study
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