EphA2 modulates radiosensitive of hepatocellular carcinoma cells via p38/mitogen‐activated protein kinase‐mediated signal pathways

Abstract

This experiment was conducted to investigate the role of EPH receptor A2 (EphA2) in the modulation of radiosensitivity of hepatic cellular cancer (HCC) cells and to determine whether p38/mitogen-activated protein kinase (p38MAPK) signaling mediated EphA2 function in this respect. The protein expressions of EphA2 and phosphorylated p38MAPK were tested in HCC and normal hepatic tissues. In HCC 97H cells, EphA2 was overexpressed and knocked out by transfection with EphA2 expression vector and EphA2-ShRNA, respectively, prior to cell exposure to low-dose irradiation. Significantly upregulated EphA2 and phosphorylated p38MAPK were observed in HCC tissues, compared with those in normal hepatic tissues. Low-dose irradiation (1 Gy) only caused minor damage to HCC 97H cells, as assessed by alterations in cell viability, apoptosis rate, and cell healing capacity (p = 0.072, p = 0.078, and p = 0.069 respectively). However, EphA2 knock-out in HCC 97H cells induced significant reduction in cell viability and cell healing capacity after these cells were subjected to low-dose irradiation. Apoptosis rate underwent dramatic increase (p < 0.01). By contrast, EphA2 overexpression in HCC 97H cells reversed these effects and enhanced cell colony formation rate, thus displaying remarkable attenuation of radiosensitivity of HCC 97H cells. Further, SB203580, a specific inhibitor of p38MAPK, was added to HCC 97H cells over-expressing EphA2. The effect of EphA2 overexpression on the radiosensitivity of HCC 97H cells was abrogated. Thus, the present study indicates that EphA2 have the ability to negatively regulate the radiosensitivity of HCC 97H cells, which mainly depends on 38MAPK-mediated signal pathways.

Influence of miR‐520e‐mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2

“…Notably, HBx has been reported to be the activator of the Src family of tyrosine kinases, which could activate the Ras‐Raf‐MAPK pathway to affect the proliferation and apoptosis of HBV‐related HCC, and at the same time, the activation of Src also enhanced the activity of viral polymerase and thereby promoting HBV replication . As we know, ERK/12 and p38MAPK are two of the most important pathways in MAPK signalling, and a previous study confirmed that EphA2 can regulate p38MAPK and ERK1/2 signalling pathway to affect cell growth . Therefore, we determined the proliferation and apoptosis of HepG2.2.15 and pHBV1.2+ Huh7 cell, as well as the expressions of pathway‐related proteins, and found that upregulation of miR‐520e inhibited cell proliferation and blocked p38MAPK and ERK1/2 pathways, whereas inhibiting miR‐520e led to completely opposite results, and si‐EphA2 reversed the effect of miR‐520e inhibitor.…”

“…Furthermore, using the target gene prediction website, we found that EphA2 was the target gene of miR‐520e, and it could regulate the MAPK signalling pathway in HCC cells, as indicated by Jin et al . More importantly, HBx has been demonstrated to participate in the development and progression of HBV‐related HCC by activating the MAPK signalling pathway .…”

“…Furthermore, using the target gene prediction website, we found that EphA2 was the target gene of miR-520e, and it could regulate the MAPK signalling pathway in HCC cells, as indicated by Jin et al 19 More importantly, HBx has been demonstrated to participate in the development and progression of HBV-related HCC by activating the MAPK signalling pathway. 20 Therefore, this study was undertaken to investigate whether miR-520e could regulate HBV replication and HCC growth by mediating the MAPK signalling pathway through targeting EphA2, hoping to provide new theoretical support for the diagnosis and treatment of HBV-related HCC.…”

“…can regulate p38MAPK and ERK1/2 signalling pathway to affect cell growth. 19 Therefore, we determined the proliferation and apoptosis of HepG2.2.15 and pHBV1.2+ Huh7 cell, as well as the expressions of pathway-related proteins, and found that upregulation of miR-520e…”

MicroRNA-145 sensitizes cervical cancer cells to low-dose irradiation by downregulating OCT4 expression

“…Wound healing assays may be used to detect cellular self-repairing capability following wound. A lower cell migration rate indicates slower proliferation and weaker self-repairing capability, which in turn suggests a higher radiosensitivity (32). Furthermore, previous studies have reported that upregulated cyclin D1 was associated a high incidence of cervical lymph node metastasis of squamous cell carcinoma (33).…”