Targeting of SPP1 by microRNA-340 inhibits gastric cancer cell epithelial-mesenchymal transition through inhibition of the PI3K/AKT signaling pathway.
Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial-mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.
Song SZ
，Lin S
，Liu JN
，Zhang MB
，Du YT
，Zhang DD
，Xu WH
，Wang HB
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Effect of microRNA-135a on Cell Proliferation, Migration, Invasion, Apoptosis and Tumor Angiogenesis Through the IGF-1/PI3K/Akt Signaling Pathway in Non-Small Cell Lung Cancer.
This study explored the ability of microRNA-135a (miR-135a) to influence cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer (NSCLC).
NSCLC tissues and adjacent normal tissues were collected from 138 NSCLC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-135a and IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 mRNA; western blotting was used to determine the expression levels of IGF-1, PI3K and Akt protein; and enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression levels of VEGF, bFGF and IL-8 protein. Human NSCLC cell lines (A549, H460, and H1299) and the human bronchial epithelial cell line (HBE) were selected. A549 cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, IGF-1 siRNA and miR-135a inhibitors + IGF-1 siRNA groups. The following were performed: an MTT assay to assess cell proliferation, a scratch test to detect cell migration, a Transwell assay to measure cell invasion, and a flow cytometry to analyze cell apoptosis.
The expression level of miR-135a was lower while those of IGF-1, PI3K and Akt mRNA were higher in NSCLC tissues than in the adjacent normal tissues. Dual-luciferase reporter assay indicated IGF-1 as a target of miR-135a. The in vitro results showed that compared with the blank group, cell proliferation, migration and invasion were suppressed, mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 were reduced, and cell apoptosis was enhanced in the miR-135a mimics and IGF-1 siRNA groups. Compared with the IGF-1 siRNA group, cells in the miR-135a inhibitors + IGF-1 siRNA group demonstrated increased cell proliferation, migration and invasion, elevated mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 and reduced cell apoptosis.
These findings indicated that miR-135a promotes cell apoptosis and inhibits cell proliferation, migration, invasion and tumor angiogenesis by targeting IGF-1 gene through the IGF-1/PI3K/Akt signaling pathway in NSCLC.
Zhou Y
，Li S
，Li J
，Wang D
，Li Q
... -
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miR-107 regulates growth and metastasis of gastric cancer cells via activation of the PI3K-AKT signaling pathway by down-regulating FAT4.
To investigate the effect of miR-107 on the growth and metastasis of gastric cancer (GC) and elucidate the probable mechanisms.
The expression of miR-107 and FAT4 in GC tissues and cells were detected using qRT-PCR. Bioinformatics and dual luciferase reporter gene assays were used to analyze the relationship between miR-107 and FAT4. miR-NC, miR-107 inhibitor, pcDNA3.1-FAT4 and siRNA-FAT4 were transfected into AGS and MKN-45 GC cell lines, respectively. The proliferation and migration abilities of GC cells after transfection were evaluated using the MTT assay, scratch test and transwell assay. The expression of epithelial-mesenchymal transition (EMT) markers: E-cadherin, N-cadherin, vimentin and related proteins of the PI3K/AKT signaling pathway were determined using western blot. The xenograft tumors of nude mice were observed to assess the tumorigenicity of GC cells in vivo.
MiR-107 was up-regulated, while FAT4 was down-regulated in GC tissues and cells (P < 0.05); FAT4 was targeted and negatively regulated by miR-107. Down-regulating miR-107 or up-regulating FAT4 inhibited the GC cells proliferation, migration, invasion and tumorigenicity, and could also reduce the expression of N-cadherin, vimentin, p-PI3K and p-Akt expression and up-regulate E-cadherin.
miR-107 promotes growth and metastasis in GC via activation of PI3K-AKT signaling by targeting FAT4, which may be a target for GC treatment.
Wang L
，Li K
，Wang C
，Shi X
，Yang H
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《Cancer Medicine》
microRNA-383 suppresses the PI3K-AKT-MTOR signaling pathway to inhibit development of cervical cancer via down-regulating PARP2.
This study aims to evaluate the effect of the regulatory relationship between microRNA-383 (miR-383) and PARP2 in the cell migration and invasion in human with cervical cancer (CC) via the PI3K-AKT-MTOR signaling pathway. Cancerous tissues and corresponding paracancerous tissues were collected from 115 patients with CC. The positive expression rate of PARP2 was detected by immunohistochemistry. HeLa cells with highest miR-383 expression were selected and assigned into the blank, negative control (NC), miR-383 mimic, miR-383 inhibitor, si-PARP2, and miR-383 inhibitor + si-PARP2 groups. qRT-PCR and Western blot were performed to evaluate the expression of miR-383, PI3K, AKT, mTOR, PARP2, and p70S6K. MTT assay were utilized to measure cell viability. Transwell assay were applied to evaluate cell invasion and metastasis. Dual luciferase reporter assay identified that PARP2 is a target gene of miR-383. Cancerous tissues manifested higher expression of PI3K, AKT, mTOR, PARP2, and p70S6K but lower miR-383 expression than paracancerous tissues. Compared with the blank and NC groups, the miR-383 mimic and si-PARP2 groups had decreased expression of PI3K, AKT, mTOR, PARP2, and p70S6K mRNA and protein. In the miR-383 mimic and si-PARP2 groups, the cell viability, migration, and invasion were descended, in comparison to the blank and NC groups. All above parameters showed an opposite trend in the miR-383 inhibitor group when compared with the blank and NC groups. This study demonstrates that miR-383 could down-regulate PARP2 to protect against CC by inhibiting PI3K-AKT-MTOR signaling pathway.
Teng P
，Jiao Y
，Hao M
，Tang X
... -
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