The qRT-PCR analysis further identified a profile of five serum miRNAs (miR-1, miR-20a, miR-27a, miR-34 and miR-423-5p) as a biomarker for GC detection.
The effects of miR-34a ectopic expression on the AKT and p-AKT expression of cisplatin-induce gastric cancer cells were determined by Western blot and flow cytometry with the PI3K pathway inhibitor Wortmannin.
In conclusion, miR-34a may act as a potential tumour suppressor in gastric cancer and is associated with the mechanisms of gastric cancer metastasis; miR-34a can inhibit gastric cancer tumourigenesis by targeting PDGFR and MET through the PI3K (phosphoinositide 3-kinase)/Akt pathway.
We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis.
In conclusion, miR‑34a was associated with the clinicopathological features of gastric cancer and was a valuable predictor of patient prognosis. miR‑34a acted as a tumor suppressor to inhibit gastric cancer proliferation and invasion via the downregulation of MET.
The regulative role of miR-335 and miR-34a over GC cell growth, apoptosis, and invasion was studied using Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay, respectively.
Therefore, we concluded that miR-34a could inhibit tumor invasion and metastasis in gastric cancer by targeting Tgif2 and may be a novel therapeutic candidate for gastric cancer.
Our study found that the expression of miR-34a was significantly decreased in DDP resistance human GC tissues and DDP resistance human GC SGC7901/DDP cells compared with normal GC tissues and cells.
Bmi-1 positively regulates stem cell-like properties via upregulating miR-21, and miR-34a negatively regulates stem cell-like characteristics by negative feedback regulation of Bmi-1 in gastric cancer.
The expression of miR-34a showed negative correlation with IGF2BP3 mRNA expression in primary GC samples and more importantly, re-overexpression of IGF2BP3 rescued the inhibitory effect of miR-34a.
Taken together, our findings support a model in which the KLF5, MYC/LINC00346/miR-34a-5p cross-talk served as critical effectors in GC tumorigenesis and progression, suggesting a new therapeutic direction in the treatment of GC.
Furthermore, miR‑34 is a novel prognostic and predictive biomarker in GC, and restoring miR‑34 expression by delivering miR‑34 mimics may be a promising therapeutic strategy for the treatment of GC.