PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126

Abstract

Protein tyrosine phosphatase non-receptor type 9 (PTPN9), also named PTP-MEG2, is an important member of the protein tyrosine phosphatase family that is involved in variety of human diseases. However, the role of PTPN9 in esophageal squamous cell carcinoma (ESCC) remains to be established. The present evaluated the potential effect and underlying mechanism of action of PTPN9 in ESCC. Immunohistochemistry was performed to detect PTPN9 protein expression in 84 ESCC tumor specimens and 30 normal esophageal tissues. The association between positive expression of PTPN9 and clinicopathological features and prognosis was analyzed. The prognostic role of PTPN9 was further investigated using multivariate regression analysis. PTPN9-small interfering RNA and microRNA (miR-126)-mimics were transfected into Eca109 cells to construct PTPN9 silencing and an miR-126 ectopic expression cell model. Reverse transcription-quantitative polymerase chain reaction, western blot analysis, cell counting kit-8, Transwell assays and flow cytometry were used to investigate the role of PTPN9 in the process of ESCC progression and its potential downstream signaling pathway. Immunohistochemical analysis revealed that PTPN9 was upregulated in ESCC tumor specimens compared with normal esophageal tissues. The χ2 test indicated that positive expression of PTPN9 was correlated with tumor node metastasis stage, tumor classification and node classification. Patients with PTPN9 positive expression had shorter survival time, compared with those that were PTPN9 negative. Multivariate regression analysis with the Cox proportional hazards regression model revealed that PTPN9 expression was a prognostic factor of overall survival for patients with ESCC. Using RNA interference, the present study demonstrated that knockdown of PTPN9 significantly suppressed cell proliferation and invasion in Eca109. Additionally, it was hypothesized that miR-126, described as a tumor suppressor in ESCC, may act at least in part via its inhibition of PTPN9 at the post-transcriptional level. To the best of our knowledge, this is the first study to demonstrate that PTPN9 is overexpressed in ESCC and associated with poor survival, and may therefore be important in the pathogenesis of ESCC.

<p>PTPN9 induces cell apoptosis by mitigating the activation of Stat3 and acts as a tumor suppressor in colorectal cancer</p>

“…The survival time is shorter in patients with positive PTPN9 expression. PTPN9 knockdown suppresses cell proliferation and invasion 21. However, the roles of PTPN9 in colorectal cancer are still inconclusive and need to be elucidated.…”

“…Decreased expression of PTPN9 can enhance cell proliferation and migration in cervical cancer and gastric cancer 19,20. Conversely, PTPN9, whose expression is upregulated in tumor tissues, facilitated cell growth and metastasis in esophageal squamous cell carcinoma 21. Nevertheless, the roles of PTPN9 in colorectal cancer and the corresponding molecular mechanism are still unknown and need to be elucidated.…”

MiR-96 enhances cellular proliferation and tumorigenicity of human cervical carcinoma cells through PTPN9

“…Moreover, PTPN9 has also been reported to promote cell proliferation and invasion in esophageal squamous cell carcinoma (ESCC) cells (Zhu et al, 2017). PTPN9 has also been observed to contribute to the invasion and metastasis in breast carcinoma (Du et al, 2013).…”

The Roles of Protein Tyrosine Phosphatases in Hepatocellular Carcinoma

“…PTPN9 is also involved in numerous cellular processes including cell proliferation, differentiation and migration through the regulation of signaling pathways [ 88 ]. Dysfunction of PTPN9 causes a variety of human diseases such as cancer [ 89 , 90 ]. The expression level of PTPN9 was significantly reduced in HCC tumor tissues compared to non-tumorous tissues.…”