mir-145-5p is a suppressor of colorectal cancer at early stage, while promotes colorectal cancer metastasis at late stage through regulating AKT signaling evoked EMT-mediated anoikis

Abstract

Background: miR-145-5P is generally considered as a tumor suppressor at early stage of colorectal cancer, but up-regulation occurs in the progressive and later stages which is associated with metastasis, indicating miR-145-5p may play dual role in colorectal cancer (CRC). To explore the detailed mechanism of miR-145-5p in carcinogenic is of importance. Methods: The expression pattern of miR-145-5p in CRC patients was downloaded from TCGA database, and the probable mechanism involved in the carcinogenic effect of miR-145-5p was predicted by bioinformatics analysis. Then, interference of miR-145-5p on SW480 and SW620 cells was conducted, and the influences on tumor cell viability, invasion ability, epithelial-mesenchymal transition (EMT), anoikis, and relative protein expression were examined respectively. Results: A total of 522 CRC patients’ data indicated that miR-145-5p expression was significantly higher in metastatic CRC than that in non-metastatic CRC, and higher expression of miR-145-5p was correlate with worse prognosis. Overexpression of miR-145-5P-5p enhanced the proliferation and invasion ability of SW620, but inhibited them in SW480. EMT was induced in SW620 after miR-145-5p overexpression and mesenchymal–epithelial transition (MET) was induced in SW480, resulted in the decreased apoptotic rate in SW620 and elevated apoptotic rate in SW480 respectively. Western blot results showed that AKT signaling pathway was involved in the miR-145-5p evoked EMT-mediated anoikis process in SW620 and SW480 cells. Conclusion: miR-145-5p is a tumor suppressor at early stage of CRC, and an oncogene at advanced stage of CRC. AKT signaling evoked EMT-mediated anoikis might be the pathway by which miR-145-5P regulates CRC cell invasion and metastasis.

Gra-CRC-miRTar: The pre-trained nucleotide-to-graph neural networks to identify potential miRNA targets in colorectal cancer

“…Similarly, miR-20a-5p enhanced the invasion and metastasis capabilities of CRC cells by inhibiting Smad4 expression, and elevated levels of miR-20a-5p were associated with a worse prognosis for patients with CRC 81 . The miR-145-5p acts as a suppressor of CRC at the early stage, while promoting CRC metastasis at a late stage through regulating AKT signaling evoked epithelial-mesenchymal transition-mediated anoikis 82 . Our results show that our model is sensitive to discovering target mRNAs whose miRNAs are validated to play critical roles in the regulation of CRC progression, which we believe could serve as an efficient tool to uncover novel dysregulated miRNAs and their targets in CRC.…”

Pan-cancer analysis reveals a regulatory pattern of anoikis in human cancers

“…We used a widely-used technique called gene set enrichment analysis (GSEA) to assess the features of Anoikis in 10422 samples across 34 types of cancer [35,36]. We demonstrated that the Anoikis score is associated with several cancer markers, namely EMT and immune [37][38][39]. The anti-tumor impact of anoikis is undeniable, and prior research has shown that it is still fundamentally a sort of apoptosis.…”

MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3

“…First, the dysregulated expression of multiple miRNAs leads to the EMT. Second, the pathways involved in the EMT include the nuclear factor kappa B, Wnt/β-catenin, and Akt pathways apart from the well-known TGF-β pathway [ 8 , 41 , 42 ]. Finally, substances such as the cytokines interferon-gamma and hypoxia-inducible factor-alpha were equally involved in the EMT [ 43 , 44 ].…”