Finally, FBXL19-AS1/miR-203a-3p axis was found to associate with baculoviral IAP repeat-containing protein 5.1-A-like (survivin), distal-less homeobox 5, E2F transcription factor 1, and zinc finger E-box binding homeobox 2 to regulate metastasis in LUAD cells.
Rescue experiments demonstrated that the inhibitory effect of miR-3653 overexpression on cell metastasis and EMT was abrogated by forced expression of Zeb2.
Emerging data indicate that ZEB2 plays a pivotal role in EMT-induced processes such as development, differentiation, and malignant mechanisms, for example, drug resistance, cancer stem cell-like traits, apoptosis, survival, cell cycle arrest, tumor recurrence, and metastasis.
Furthermore, in an orthotopic tumor transplantation model in vivo, HBx promoted tumor growth and metastasis, whereas the knockdown of SIP1 attenuated the effect of HBx.
Furthermore, H19 overexpression inhibited miR-200a function and thereby upregulated miR-200a target genes, ZEB1 and ZEB2.H19 sponged and inhibited miR-200a to de-repress expression of ZEB1 and ZEB2, and thereby enhanced lung cancer proliferation and metastasis.
These findings add another level of complexity to the understanding of ZEB2 in the invasion and metastasis of cancer cells, and put ZEB2/ETS1 axis as a novel therapeutic target in human malignancies.
Thus, with previous experimental evidences, the present review discussed the role of FoxOs in association with metastasis related molecules including cannabinoid receptor 1 (CNR1), Cdc25A/Cdk2, Src, serum and glucocorticoid inducible kinases (SGKs), CXCR4, E-cadherin, annexin A8 (ANXA8), Zinc finger E-box-binding homeobox 2 (ZEB2), human epidermal growth factor receptor 2 (HER2) and mRNAs such as miR-182, miR-135b, miR-499-5p, miR-1274a, miR-150, miR-34b/c and miR-622, subsequently analyzed the molecular mechanism of some natural compounds targeting FoxOs and finally suggested future research directions in cancer progression and metastasis.
Both miR-30a-5p and -3p showed the capacity of targeting ZEB2, a transcription factor involved in epithelial-mesenchymal transition (EMT), tumor cell migration and drug resistance.
This study suggests that invasion is linked to cancer cell survival and angiogenesis by ZEB2 during cancer progression, and increases our understanding of the pathways via which EMT-inducing transcription factors regulate the complex process of metastasis.
And then, we detected that expression level of ZEB2, a transcription factor related to tumor metastasis, was regulated by UCA1 in GC cells. miR-203 targets and suppresses to ZEB2 expression.
Our observation that ZEB2 negatively regulates a GalNAc-transferase (GALNT3) that is involved in O-glycosylation adds another layer of complexity to the role of ZEB2 in cancer progression and metastasis.
The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.
MicroRNA (miRNA)-200c and miRNA-141 are tumour suppressors, which regulate epithelial-mesenchymal transition (EMT), leading to tumour invasion and metastasis in various malignancies. miRNA-200c and miRNA-141 maintain the epithelial phenotype by post-transcriptionally inhibiting the E-cadherin repressors, zinc finger E-box binding homeobox (ZEB)1 and ZEB2.