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 ... -  《-》

MicroRNA-99b suppresses human cervical cancer cell activity by inhibiting the PI3K/AKT/mTOR signaling pathway.

Cervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of miR-99b-5p (miR-99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray-based analysis was used to screen out differentially expressed miRNAs. Expression of miR-99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR-99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR-99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR-99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR-99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR-99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment.

Li YJ ，Wang Y ，Wang YY 《-》

microRNA-944 inhibits breast cancer cell proliferation and promotes cell apoptosis by reducing SPP1 through inactivating the PI3K/Akt pathway.

Breast cancer is a common malignancy in women with poor prognosis. This study aimed to investigate the molecular mechanism of microRNA-944 (miR-944) mediated secreted phosphoprotein-1 (SPP1) in breast cancer progression and its regulatory effect on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Differential gene analysis was performed to identify key genes associated with breast cancer development by screening breast cancer-related microarray data. The expression of miR-944 and SPP1 and their relationship were determined in clinical samples and cells. sh-SPP1, oe-SPP1, LY294002 or miR-944 mimic were transfected into MCF-7 cells to investigate the role of miR-944 mediated SPP1 in breast cancer development and its regulatory effect on the PI3K/Akt pathway. Finally, the tumorigenicity of breast cancer cells was observed in nude mice. Through bioinformatics analysis, we identified SPP1 as a key gene in breast cancer, and miR-944 as an upstream miRNA of SPP1. In breast cancer tissues and cells, the expression of miR-944 was decreased while that of SPP1 was increased. miR-944 negatively regulated the expression of SPP1. In breast cancer cells, SPP1 activated the PI3K/Akt pathway to promote cell proliferation and inhibit apoptosis. In vitro cell experiments showed that the downregulation of miR-944 promoted the high expression of SPP1, which then activated the PI3K/Akt signaling pathway, promoting breast cancer cell proliferation. In vivo experiments further confirmed the anti-cancer role of miR-944 mediated SPP1 in breast cancer. Our study highlights the role of miR-944 mediated SPP1 in inhibiting breast cancer progression by blocking the PI3K/Akt pathway.

Zhang Y ，Li S ，Cui X ，Wang Y ... -  《-》

High expression of TCF12 contributes to gastric cancer development via being target regulated by miR-183 and activating PI3K/AKT pathway.

This study aimed to explore the role of transcription factor 12 (TCF12) in the process of gastric cancer (GC) and to elucidate its possible regulatory mechanism. The expression data of GC tissues and matched normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Survival analysis for GC patients with different levels of TCF12 was performed by the Kaplan-Meier analysis. In addition, TCF12 was suppressed in human GC cell lines AGS and MKN-45, followed by detecting cell biological processes (proliferation, apoptosis, migration, and invasion). Moreover, the association between TCF12 and the phosphatidylinositol 3-kinase (PI3K)/AKT signal was elucidated. Besides, the potential micro RNAs that could target TCF12 expression were explored. The results showed that TCF12 was highly expressed in GC tissues and TCF12 upregulation was associated with poor prognosis of GC patients. In addition, suppression of TCF12 significantly inhibited the proliferation, migration, and invasion of both AGS and MKN45 cells, as well as induced apoptosis of the two cell lines. Moreover, suppression of TCF12 significantly decreased the expression of p-AKT, cyclin D1, p-P70, and β-catenin in both AGS and MKN45 cells. Besides, TCF12 was target regulated by miR-183 in GC cells. Our findings reveal that TCF12 is upregulated in GC and its upregulation is associated with poor prognosis of GC patients. To sum up, downregulation of TCF12 may inhibit GC development via being target regulated by miR-183 and inhibiting the PI3K/AKT signal. TCF12 may function as a potential therapeutic target for GC.

Wang X ，Gao S ，Xie F ，Li W ，Li M ，Yan N ，Gao T ，Fang L ... -  《-》

MicroRNA-203 inhibits epithelial-mesenchymal transition, migration, and invasion of renal cell carcinoma cells via the inactivation of the PI3K/AKT signaling pathway by inhibiting CAV1.

Han N ，Li H ，Wang H 《-》