MiR-141-3p is upregulated in esophageal squamous cell carcinoma and targets pleckstrin homology domain leucine-rich repeat protein phosphatase-2, a negative regulator of the PI3K/AKT pathway.

The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is frequently activated in various human cancers and plays essential roles in their development and progression. Accumulating evidence suggests that dysregulated expression of microRNAs (miRNAs) is closely associated with cancer progression and metastasis. Here, we focused on miRNAs that could regulate genes related to the PI3K/AKT pathway in esophageal squamous cell carcinoma (ESCC). To identify upregulated miRNAs and their possible target genes in ESCC, we performed microarray-based integrative analyses of miRNA and mRNA expression levels in three human ESCC cell lines and a normal esophageal epithelial cell line. The miRNA microarray analysis revealed that miR-31-5p, miR-141-3p, miR-200b-3p, miR-200c-3p, and miR-205-5p were expressed at higher levels in the ESCC cell lines than the normal esophageal epithelial cell line. Bioinformatical analyses of mRNA microarray data identified several AKT/PI3K pathway-related genes as candidate targets of these miRNAs, which include tumor suppressors such as DNA-damage-inducible transcript 4 and pleckstrin homology domain leucine-rich repeat protein phosphatase-2 (PHLPP2). To validate the targets of relevant miRNAs experimentally, synthetic mimics of the miRNAs were transfected into the esophageal epithelial cell line. Here, we report that miR-141-3p suppress the expression of PHLPP2, a negative regulators of the AKT/PI3K pathway, as a target in ESCC.

Ishibashi O ，Akagi I ，Ogawa Y ，Inui T ... -  《-》

Expression and role of oncogenic miRNA-224 in esophageal squamous cell carcinoma.

He X ，Zhang Z ，Li M ，Li S ，Ren L ，Zhu H ，Xiao B ，Shi R ... -  《BMC CANCER》

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》

The CADM2/Akt pathway is involved in the inhibitory effect of miR-21-5p downregulation on proliferation and apoptosis in esophageal squamous cell carcinoma cells.

Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer, is the eighth most common cancer worldwide. Cell adhesion molecule 2 (CADM2) has been reported to be a tumor suppressor and is usually downregulated in several cancers. However, the role of CADM2 in ESCC remains unknown. The aim of the present study was to evaluate the potential role and underlying action mechanism of CADM2 in ESCC. Herein, we found that CADM2 was low-expressed in ESCC tissues and cell lines. CADM2 overexpression inhibited proliferation and induced apoptosis of ESCC cells. Moreover, CADM2 overexpression also suppressed the Akt signaling pathway in ESCC cells. MiR-21-5p down-regulation inhibited cell proliferation and induced cell apoptosis, while CADM2 knockdown attenuated the effect of anti-miR-21-5p. The expression of p-Akt was decreased in the cells transfected with anti-miR-21. However, the expression of p-Akt was increased in the cells co-transfected with anti-miR-21-5p and si-CADM2 compared with that in anti-miR-21-5p-transfecting cells. In summary, the CADM2/Akt pathway is involved in the inhibitory effect of miR-21-5p downregulation on proliferation and apoptosis in ESCC cells. These findings indicated that the miR-21-5p/CADM2/Akt axis might be a new approach for the treatment of ESCC.

Li X ，Chen D ，Li M ，Gao X ，Shi G ，Zhao H ... -  《-》

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 ... -  《-》