miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis.

Esophageal squamous cell carcinoma (ESCC) is one of the lethal cancers with a high incidence rate in Asia. Cyclin D1 is overexpressed and plays an important role in the carcinogenesis of ESCC; however the mechanism of the deregulation of Cyclin D1 in ESCC remains to be determined. In the study, we found that miR-18a promotes the expression Cyclin D1 by targeting PTEN in eophageal squamous cell carcinoma TE13 and Eca109 cells. Transfection of miR-18a mimetics increased cyclin D1, while transfection of miR-18a antagomir decreased D1. Moreover, miR-18a-mediated upregulation of cyclin D1 was accompanied with downregulation of PTEN, which is a direct target of miR-18a, and increase of the phosphorylation of AKT and S6K1. In addition, pharmacologic inhibition of AKT or mTOR kinases abolished the increase of cyclinD1 by miR-18a, which was accompanied with decreased phosphorylation of RbS780 and inhibition of cell proliferation. Our results demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster.

Zhang W ，Lei C ，Fan J ，Wang J ... -  《-》

MiR-214 promotes cell meastasis and inhibites apoptosis of esophageal squamous cell carcinoma via PI3K/AKT/mTOR signaling pathway.

There is growing evidence shown that microRNAs (miRNAs) are associated with cancer and can play a role in human cancers as oncogenes or tumor suppressor genes. MicroRNA-214 (miR-214) shows carcinogenesis in various tumor types, but little is known about biological functions of miR-214 in esophageal squamous cell carcinoma (ESCC). In this study, we observe that the expression of miR-214 is not only increased in human ESCC tissues, but also remarkably increased in cell lines correlates with LZTS1. In addition, the expression of miR-214 inhibited proliferation of ESCC cells in vitro and inhibit the growth of xenograft tumor in vivo. The results show miR-214 serve as a tumor promoter regulating cells migration, invasion and apoptosis in ESCC. Ferthermore, LZTS1 has been proved to as a functional target for miR-214 to regulate cells poliferation and apoptosis. In summary, these results suggest that miR-214 serves as tumor promoter to promote proliferation, migration, invasion and inhibit apoptosis of ESCC cells by targeting LZTS1 via PI3K/AKT/mTOR signaling pathway. The miR-214/LZTS1 pathway provides a new insight into the molecular mechanisms that the occurrence and development of ESCC and it provides a novel therapeutic target for ESCC.

Guanen Q ，Junjie S ，Baolin W ，Chaoyang W ，Yajuan Y ，Jing L ，Junpeng L ，Gaili N ，Zhongping W ，Jun W ... -  《-》

Osthole inhibits the PI3K/AKT signaling pathway via activation of PTEN and induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors and is known to be lack of effective therapy. Thus, novel therapeutic strategies are greatly needed for treatment of ESCC. Osthole, a natural active extract, has been documented to have anti-tumor activity. However, the effect of osthole on ESCC cells has not been elucidated. In this study, we demonstrated that osthole could inhibit the ESCC cell proliferation in dose- and time-dependent manner. Osthole treatment also induced G2/M phase arrest and apoptosis of ESCC cells. Furthermore, upon exposure to osthole, the expression of Cyclin B1, Cdc2, Bcl-2, PARP1 and Survivin was decreased, while the expression of BAX, cleaved PARP1, cleaved Caspase3 and cleaved Caspase9 was increased. In addition, osthole treatment elicited upregulation of PTEN and downregulation of PI3K and phosphorylated AKT (p-AKT). Taken together, our study demonstrates that osthole could suppress ESCC proliferation through inducing cell cycle arrest and apoptosis. Moreover, PTEN-PI3K/AKT signaling pathway can be regulated by osthole. Our results indicate that osthole may find therapeutic application in the treatment of ESCC patients.

Zhu X ，Li Z ，Li T ，Long F ，Lv Y ，Liu L ，Liu X ，Zhan Q ... -  《-》

siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin.

Hasan R ，Chauhan SS ，Sharma R ，Ralhan R ... -  《-》

MiR-130b plays an oncogenic role by repressing PTEN expression in esophageal squamous cell carcinoma cells.

Yu T ，Cao R ，Li S ，Fu M ，Ren L ，Chen W ，Zhu H ，Zhan Q ，Shi R ... -  《BMC CANCER》