Lack of miR‐1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2

Abstract

Small extracellular vesicle (sEV) has precise impacts on tumor microenvironment and play vital functions in intercellular interaction. However, the functional role of sEV miRNA on laryngeal squamous cell carcinoma (LSCC) is largely unresolved. Here, the expression of miR‐1246 in LSCC tissues and plasma sEV was examined. The internalization ability of sEV was determined by uptake assay. Then, the source and purity of sEV were checked through RNase and/or pharmacological inhibitors application. The invasion, migration, proliferation, and cell cycle assays were used to determine the altered abilities of miR‐1246 in sEV in LSCC. Finally, target gene of miR‐1246, Cyclin G2 (CCNG2), was stained immunohistochemically. In addition, the relationship between CCNG2 and clinicopathological features of patients was analyzed. We found that miR‐1246 was higher in LSCC tissues and plasma sEV. MiR‐1246 was enriched in sEV rather than soluble form. SEV could be internalized into adjacent cells. Lack of miR‐1246 in sEV abrogated the tumorigenesis of LSCC. Furthermore, CCNG2 knockdown arrested the cell cycle and correlated to clinicopathological features and prognosis of LSCC patients. Taken together, we found that the function of sEV miR‐1246 by regulating CCNG2 is responsible for LSCC advancement with emphasis on the main source of miR‐1246 mainly root in sEV rather than in soluble form.

MicroRNA-1246 by Targeting AXIN2 and GSK-3β Overcomes Drug Resistance and Induces Apoptosis in Chemo-resistant Leukemia Cells

“…Overexpression of miR-1246 promoted UVB-induced apoptosis in HaCaT cells [38]. Previous results indicated that lack of miR-1246 arrested the cell cycle at the G0/G1 phase [32]. Similar to that, our cell cycle distribution assay proved that loss of miR-1246 could halt cells at the G0/G1 phase in chemo-resistant leukemia cells (Figure 2E).…”

“…After Annexin V-FITC and PI staining, the data checked by flow cytometry showed that loss of miR-1246 promoted cell apoptosis, and this was statistically significant (Figure 2D). Similar to previous cell cycle results at the small extracellular vesicle level [32], lack of miR-1246 in chemo-resistant leukemia cells repressed the advancement of cell cycle by halting cells at the G0/G1 phase. While ADM treatment led to cell cycle arrest and the accumulation of cells at the G2/M phase (Figure 2E).…”

miR-17-5p drives G2/M-phase accumulation by directly targeting CCNG2 and is related to recurrence of head and neck squamous cell carcinoma

“…Although most of the evidence in the literature supports a role for CCNG2 in limiting G1/S phase transition [ 23 , 24 ], there are indications that CCNG2 could participate in G2/M regulation [ 23 , 25 , 26 ]. We previously proved that CCNG2 siRNA application in LSCC cell lines contributes to the increased G2/M phase proportion [ 16 ]. This is consistent with our findings that the overexpression of CCNG2 in FaDu cells led to a decrease in the G2/M phase proportion.…”

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A Review on the Role of miR-1246 in the Pathoetiology of Different Cancers

“…Lack of miR-1246 in these vesicles abolished development of this kind of cancer. miR-1246 content of small vesicles could participate in the pathoetiology of laryngeal squamous cell carcinoma through suppressing CCNG2 expression ( Huang Q. et al, 2020 ). miR-1246 is involved in the progression of melanoma via changing expression levels FOXA2 ( Yu et al, 2020 ).…”