MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer

Abstract

It has been reported that miR-19a was up-regulated in gastric cancer (GC), playing an oncogenic role. However, the underlying mechanism is still unknown. Therefore, in our present study, we investigated the role of miR-19a in gastric tissues as well as 2 GC cell lines. In vivo in clinical tissue level, we have detected basal expression level of miR-19a using real-time reversal transcriptional PCR (RT-PCR); in addition, the relevance between expression of miR-19a and clinic-pathological information was also analyzed. In vitro in cell line level, miR-19a was ectopically expressed using over expression and knock-down strategy. It was found that the overexpression of miR19a was significantly associated with metastasis of GC and inferior overall prognosis on clinical tissue level; that promotes the proliferation, migration and invasion; and that overexpression of miR-19a can promote the epithelialmesenchymal transition through activating PI3K/AKT pathway. Blocking the PI3K/AKT pathway could cancel the effect of miR-19a. All together, our results suggest that miR-19a could be used as a promising therapeutic target in the treatment of GC.

miRNA-223 inhibits epithelial-mesenchymal transition in gastric carcinoma cells via Sp1

“…Zhang et al reported that Wnt5a, through stimulation of the non-classical Wnt signaling pathway, mediates EMT during the metastasis of cancer cells, and may serve as a target for the inhibition of EMT and gastric cancer metastasis (32). Lu et al have shown that miRNA-19a, which is associated with cancer invasion and metastasis and is expressed highly in gastric cancer cell lines, induces EMT in gastric cancer cells by activating the PI3K/AKT signal pathway (33 (12). Previous study by Nam and colleagues on cancer cell EMT has shown that Sp1 plays crucial roles in the integrin α5-dependent induction of EMT and metastasis (8).…”

Stress Chaperone Mortalin Contributes to Epithelial-to-Mesenchymal Transition and Cancer Metastasis

“…The proinvasive and prometastasis effects of sorafenib (antiangiogenic agent that inhibits tumor growth but promotes tumor invasion and metastasis in HCC) were assigned to activate PI3K/Akt/snail pathway (45). Overexpression of miR19a was also shown to activate PI3K/AKT signaling, and induced EMT in gastric cancers (43). Overexpression of mortalin was earlier shown to inactivate p53, activate telomerase, and antiapoptotic signaling through Raf/MEK/ERK pathway and inhibition of conformational change of Bax (17,18,38), and to mediate erythropoietin-induced growth of erythroid progenitor cells ( Fig.…”

“…4). PI3K-Akt signaling has been reported to regulate EMT through the transcription factor snail, a critical EMT mediator (43,44). The proinvasive and prometastasis effects of sorafenib (antiangiogenic agent that inhibits tumor growth but promotes tumor invasion and metastasis in HCC) were assigned to activate PI3K/Akt/snail pathway (45).…”

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5

“…To our knowledge, the present study is the first to provide evidence that PITX1 expression is modulated through miR-19a-3p in GC. miR-19a is frequently overexpressed, promotes cell proliferation and the epithelial to mesenchymal transition, and inhibits cell apoptosis in lung carcinoma [36,37], osteosarcoma stem cells [38], colorectal cancer [39][40][41][42], cell renal cell carcinoma [43], oral squamous cell carcinoma [44], hepatocellular carcinoma cells [45], pancreatic cancer [46], GC [47,48], cholangiocarcinoma [49], breast cancer [50], bladder cancer [51], medulloblastoma [52], and cervical carcinoma [53]. Our findings are consistent with these data because they provide evidence that miR19a is a key regulator of the multistep processes of cancer development.…”