MiR-200c-3p aggravates gastric cell carcinoma via KLF6

Abstract

Background Gastric cell carcinoma (GCC) is a common and high-incidence malignant gastrointestinal cancer that seriously threatens human life and safety. Evidences suggest that microRNAs (miRNAs) exhibit an essential role in regulating the occurrence and development of GCC, while the effects and possible mechanisms remain to be further explored. Objective This study was designed to explore whether miR-200c-3p exerted its functional role in the growth and metastasis of GCC, and investigate the possible mechanisms. Methods The expression levels of miR-200c-3p in GCC tissues and cell lines were detected by qRT-PCR analysis. The functional role of miR-200c-3p in the viability, proliferation, migration and invasion of GCC cells were evaluated by CCK-8, EdU, wound healing and Transwell assays. In addition, the candidate targets of miR-200c-3p was predicted and confirmed by dual-luciferase reporter assay. Moreover, the relationship between miR-200c-3p and target (Krüppel like factor 6, KLF6) was assessed by qRT-PCR and western blot assays. Besides, the expression levels of KLF6 in GCC cells were determined by qRT-PCR and western blot assays. Furthermore, the role of KLF6 in the viability, proliferation, migration and invasion of GCC cells mediated with miR-200c-3p mimics was evaluated by CCK-8, EdU, wound healing and Transwell assays. Results In the present study, a new tumor promoting function of miR-200c-3p was disclosed in GCC. We found that the expression of miR-200c-3p was obviously increased in clinic GCC tissues and cell lines. In addition, down-regulation of miR-200c-3p suppressed cell viability, proliferation, migration, and invasion in GCC cells. Moreover, KLF6 was verified as a direct target of miR-200c-3p by binding its 3’-UTR. Additionally, KLF6 was remarkably decreased and was negatively associated with the miR-200c-3p expression in GCC cell lines. Furthermore, over-expression of KLF6 retarded the effects of miR-200c-3p on the growth and metastasis of GCC cell lines. Conclusions MiR-200c-3p potentially played a tumor-promoting role in the occurrence and development of GCC, which may be achieved by targeting KLF6. Graphic abstract

The tumor suppressor effect of miRNA 200-c-3p on A549 non-small cell lung cancer cell line is associated with down-regulation of programmed cell death ligand 1; an immune-check point mechanism

“…It was found that miRNA 200-c-3p can act as a positive or negative regulator of epithelial-mesenchymal transition (EMT) in different cells and tissue types [20][21][22]. MiRNA 200-c-3p can modulate tumor proliferation, invasion and metastasis by acting differentially on the EMT process [23][24][25]. Due to its differential expression and actions in various tissue and cells, miRNA 200-c-3p is reported as being either a tumor-suppressive or an oncogenic miRNA in many cancer types [24,25].…”

miRNAs as short non-coding RNAs in regulating doxorubicin resistance

“…After the discovery of miRNAs and by advances in field of biology and next generation sequencing, miRNA's role in diseases and cancer was evaluated (Zhang et al 2021b; Li et al 2021c; Tanaka et al 2021; Xie et al 2021). It has been shown that miRNA‐200c‐3p increases growth and invasion of gastric tumor by KLF6 suppression (Wang et al 2021a). miRNA‐199b‐5p‐induced EMT enhances metastasis by HHIP inhibition (Chen et al 2021a).…”

Immunosuppressive landscape in hepatocellular carcinoma revealed by single-cell sequencing

“…We found that compared to other clusters, cluster 1 and cluster 4 had higher expression of KLF6, PRDM1, STAT1, JUNB, and HES1 (Figure 3I). Researchers have reported that KLF6 plays an essential role in immunosuppression and modulates neutrophil maturation (38)(39)(40)(41)(42), while PRDM1 is a crucial epigenetic gene associated with T-cell terminal differentiation (43,44). In other words, targeting PRDM1 would enable the generation of superior antitumor T cells.…”