SOX9/miR-203a axis drives PI3K/AKT signaling to promote esophageal cancer progression.

Deregulation of SOX9 in esophageal cancer has been reported. However, the regulatory mechanisms underlying SOX9 during esophageal squamous cell carcinoma (ESCC) progression remain poorly understood. Here, we independently confirmed the increased SOX9 expression in two ESCC cohorts and its correlation with poor prognosis. We demonstrated that SOX9 was required for maintaining self-renewal, motility, and chemoresistance in vitro and that ectopic expression of SOX9 promoted tumorigenicity in vivo. Screening for potential SOX9-regulated miRNAs revealed that target genes of differentially expressed miRNAs were enriched in the PI3K/AKT signaling pathway and identified the downregulated miR-203a as a candidate. Mechanistically, SOX9 activation caused repression of miR-203a transcription by binding to miR-203a promoter, thus preventing the miR-203a-mediated inhibition of multiple PI3K/AKT/mTOR components, including PIK3CA, AKT2, and RPS6KB1. The association between SOX9 expression and PI3K/AKT/mTOR signaling was further validated in clinical samples. Moreover, rapamycin treatment attenuated the SOX9-mediated malignant phenotypes and potentiated cisplatin-mediated inhibition of tumor growth. Together, these findings uncover a novel activation of the PI3K/AKT pathway by the SOX9/miR-203a axis and define a subgroup of patients who may benefit from targeted therapy.

Wang L ，Zhang Z ，Yu X ，Li Q ，Wang Q ，Chang A ，Huang X ，Han X ，Song Y ，Hu J ，Pang L ，Hou J ，Li F ... -  《-》

Upregulation of miR-519 enhances radiosensitivity of esophageal squamous cell carcinoma trough targeting PI3K/AKT/mTOR signaling pathway.

Zhang Y ，Chen W ，Wang H ，Pan T ，Zhang Y ，Li C ... -  《-》

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 ... -  《-》

LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1.

Chang ZW ，Jia YX ，Zhang WJ ，Song LJ ，Gao M ，Li MJ ，Zhao RH ，Li J ，Zhong YL ，Sun QZ ，Qin YR ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

CircVRK1 regulates tumor progression and radioresistance in esophageal squamous cell carcinoma by regulating miR-624-3p/PTEN/PI3K/AKT signaling pathway.

As a novel class of noncoding RNAs (ncRNAs), circular RNAs (circRNAs) have been verified to be potential biomarkers and therapeutic targets for human malignant tumors. However, the thorough understanding of circRNAs in the progression of esophageal squamous cell carcinoma (ESCC) still needs to be improved. This study focused on exploring the function and mechanism of circVRK1 in ESCC. At first, we examined the expression level of circVRK1 in ESCC tissues and cell lines with qRT-PCR. We found that circVRK1 was downregulated in ESCC tissues and cell lines. Kaplan-Meier method was used to analyze the correlation between circVRK1 expression and the overall survival of ESCC patients. Functionally, overexpression of circVRK1 suppressed the cell proliferation, migration and epithelial-mesenchymal transition (EMT) and reversed the radioresistance. Therefore, we identified the tumor suppressive role of circVRK1 in ESCC progression. Mechanistically, circVRK1 positively regulated PTEN by acting as a molecular sponge of miR-624-3p. Moreover, circVRK1 decreased the activity of PI3K/AKT signaling pathway by upregulating PTEN. Rescue assays were carried out to confirm the function of circVRK1-miR-624-3p-PTEN axis in ESCC progression. Our findings showed that circVRK1 suppressed ESCC progression by regulating miR-624-3p/PTEN axis and PI3K/AKT signaling pathway, suggesting the potential therapeutic value of circVRK1 for ESCC.

He Y ，Mingyan E ，Wang C ，Liu G ，Shi M ，Liu S ... -  《-》