microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway

Abstract

MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and proliferation during CRC in addition to their underlying mechanisms. CRC tissues and colon cancer cell lines (SW620 and HCT8) were investigated. qRT-PCR and Western blot were utilized to evaluate miR-16-5p and FOXK1 expression. Following gain- and loss-of-function assays on miR-16-5p or FOXK1, the effects of miR-16-5p and FOXK1 were assessed on cell angiogenesis and proliferation in CRC cells. A dual-luciferase reporter assay was employed to evaluate the binding relationship of miR-16-5p and FOXK1. Western blot was used to determine the effects of miR-16-5p and FOXK1 on key molecules of the PI3K/Akt/mTOR pathway. Highly expressed FOXK1 and lowly expressed miR-16-5p were observed in CRC cells and tissues. miR-16-5p overexpression or FOXK1 knockdown reduced CRC cell proliferation and angiogenesis of human umbilical vein endothelial cells co-cultured with the supernatant of CRC cells, whereas miR-16-5p silencing or FOXK1 upregulation caused opposite trends. Additionally, miR-16-5p negatively modulated FOXK1 expression. The blockade of the PI3K/Akt/mTOR pathway was triggered by miR-16-5p overexpression or FOXK1 silencing. In conclusion, miR-16-5p hampers cell angiogenesis and proliferation during CRC by targeting FOXK1 to block the PI3K/Akt/mTOR pathway.

Network Pharmacology-Integrated Molecular Docking Reveals the Expected Anticancer Mechanism of Picrorhizae Rhizoma Extract

“…PTGS2 is a target associated with cervical cancer, pancreatic ductal adenocarcinoma, nasopharyngeal carcinoma, and colorectal cancer [42][43][44][45]. MTOR [45][46][47][48][49][50][51][52] is a target associated with breast cancer, bladder cancer, hysteromyoma, laryngeal cancer, kidney cancer, liver cancer, thy-roid cancer, epidermoid squamous cell carcinoma, and colorectal cancer.…”

Chemopreventive Effect on Human Colon Adenocarcinoma Cells of Styrylquinolines: Synthesis, Cytotoxicity, Proapoptotic Effect and Molecular Docking Analysis

“…Compound 3a presented a significant inhibition of cell proliferation at lower concentrations than those required by compound 3d , which may have been due to the difference in the number of functional groups and their positions in the structure of each hybrid, which provided them different properties and reactivity. Furthermore, greater cytotoxicity of the treatments was observed in the SW620 cell line, possibly because it has been described that SW480 and SW620 cells present differences in the karyotype and expression profile of microRNAs, which have been associated with CRC progression through regulation of some signaling pathways and with chemoresistance to some drugs [ 43 , 44 , 45 , 46 ]. In the same sense, it has been seen that certain post-translational modifications of some cellular proteins have been gaining importance in the study of many diseases, including different types of cancer [ 47 ].…”

Noncoding RNAs and programmed cell death in hepatocellular carcinoma: Significant role of epigenetic modifications in prognosis, chemoresistance, and tumor recurrence rate

“…Another type of ncRNA, miRNAs, contributes to inhibiting tumor T A B L E 1 The comparison of apoptosis, ferroptosis, and necroptosis processes in terms of biochemical properties, main proteins, cell membrane, cell morphology, and nucleus (Hosohata et al, 2022). ways in colorectal cancer (Huang et al, 2022). CircRNAs are described as vital modulators of cancer advancement and T A B L E 2 Some recognized tumor markers usable for hepatocellular carcinoma.…”

“…Another type of ncRNA, miRNAs, contributes to inhibiting tumor growth and regulating gene targets in metastasis and oncogenesis (Petri & Klinge, 2020). MiRNAs function a systematized role in angiogenesis, metastasis, apoptosis, autophagy, and regulating associated signing pathways, such as the extracellular signal‐regulated kinase (ERK)/MAPK, Wnt/β‐catenin, and phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways in colorectal cancer (Huang et al, 2022). CircRNAs are described as vital modulators of cancer advancement and proliferation‐associated signaling (Nisar et al, 2021).…”