EGFR Promoter Methylation, EGFR Mutation, and HPV Infection in Chinese Cervical Squamous Cell Carcinoma

Zhang, Wei; Jiang, Yinghao; Yu, Qingmiao; Qiang, Shaoying; Liang, Ping; Gao, Yue; Zhao, Xingye; Li, Wenchao; Zhang, Ju

doi:10.1097/pai.0000000000000128

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…To understand how miR-133a facilitates cervical cancer growth and metastasis, we used two algorithms (Targetscan and miRanda) to help identify miR-133a targets in human cervical cancers. EGFR was selected from several putative miR-133a target genes, since IGF-1R has been shown to be involved in tumorigenesis and metastasis (19,20). As shown in Fig.…”

Section: Overexpression Of Mir-133a Inhibits the Migration And Invasimentioning

confidence: 99%

miR-133a inhibits cervical cancer growth by targeting EGFR

et al. 2015

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MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in cervical carcinogenesis and progression. microRNA-133a (miR-133a) has been reported to play a tumor-suppressor role in a range of cancers. However, the role and underlying molecular mechanism of miR-133a in cervical cancer have not been investigated. In the present study, we investigated the role of miR-133a in the tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-133a was investigated using real-time reverse transcription-polymerase chain reaction (qRT-PCR) in 30 cervical specimens and matched adjacent normal tissues and cervical cancer cell lines. We found that the expression level of miR‑133a was significantly downregulated in cervical cancer tissues and cervical cancer cell lines, and the aberrant expression of miR-133a was correlated with lymph node metastasis, histological grade and FIGO stage. The role of miR-133a in tumorigenicity of cervical cancer cells was assessed by the restoration of miR-133a. We found that restoration of miR‑133a inhibited cell proliferation, colony formation, migration and invasion, promoted cell apoptosis in vitro and suppressed tumorigenicity in vivo. The epidermal growth factor receptor (EGFR) was confirmed to be a direct target of miR-133a in cervical cancer cells using luciferase assay and western blotting. Restoration of miR-133a inhibited EGFR expression and activated the AKT and ERK signaling pathways. These results showed that miR-133a suppresses cervical cancer growth in vitro and in vivo through targeting EGFR, suggesting that miR-133a can be a potential target for the treatment of cervical cancer.

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Section: Overexpression Of Mir-133a Inhibits the Migration And Invasimentioning

confidence: 99%

miR-133a inhibits cervical cancer growth by targeting EGFR

et al. 2015

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“…Activation of EGFR regulates gene transcription and modulates cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis through MEK-extracellular signal-regulated kinase1/2 (ERK1&2) kinase pathway or PI3K-AKT pathway [ 22 ]. Recently reports showed that EGFR was overexpressed in cervical biopsies of cervical cancer patients [ 5 , 23 ]. The number of biopsies with intense immunoexpression of EGFR increased with the severity of cytological abnormality.…”

Section: Discussionmentioning

confidence: 99%

“…EGFR is a member of the ErbB family, tyrosine kinase receptors with growth promoting effects which play a significant role in signaling pathways including cell proliferation, angiogenesis, and tumor progression [ 3 – 5 ]. Overexpression of EGFR signaling has been linked to the majority of cancers.…”

Section: Introductionmentioning

confidence: 99%

Effects of Tetrahydrocurcumin on Tumor Growth and Cellular Signaling in Cervical Cancer Xenografts in Nude Mice

Yoysungnoen

Bhattarakosol

Changtam

et al. 2016

BioMed Research International

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Tetrahydrocurcumin (THC) is a stable metabolite of curcumin (CUR) in physiological systems. The mechanism underlying the anticancer effect of THC is not completely understood. In the present study, we investigated the effects of THC on tumor growth and cellular signaling in cervical cancer xenografts in nude mice. Cervical cancer cells (CaSki) were subcutaneously injected in nude mice to establish tumors. One month after the injection, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. Relative tumor volume (RTV) was measured every 3-4 days. COX-2, EGFR, p-ERK1&2, p-AKT, and Ki-67 expressions were measured by immunohistochemistry whereas cell apoptosis was detected by TUNELS method. THC treatments at the doses of 100, 300, and 500 mg/kg statistically retarded the RTV by 70.40%, 76.41%, and 77.93%, respectively. The CaSki + vehicle group also showed significantly increased COX-2, EGFR, p-ERK1&2, and p-AKT; however they were attenuated by all treatments with THC. Ki-67 overexpression and a decreasing of cell apoptosis were found in CaSki + vehicle group, but these findings were reversed after the THC treatments.

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“…Cervical cancer (CC) is the fourth most common tumor type and leading cause of cancer death among women worldwide. Its incidence rate has increased in recent years (1,2). Thus, to develop better prognostic and therapeutic strategies for CC, insight into the molecular and biologic mechanisms of tumorigenesis is critical.…”

Section: Introductionmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) was reported to correlate with cervical cancer (13). Overactivation of EGFR signaling is a hallmark of cancer and therapy strategy toward EGFR inhibition in cervical cancer has been ongoing (1). However, signaling proteins that connect the EGFR oncogenic cascade are poorly characterized (14).…”

Section: Introductionmentioning

confidence: 99%

EBP50 interacts with EGFR and regulates EGFR signaling to affect the prognosis of cervical cancer patients

Peng

Wang

Zhang

et al. 2016

International Journal of Oncology

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Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) has a role in the occurrence and progression of multiple types of tumors. However, its role in cervical cancer (CC) remain unknown. EBP50 was reported to interact with epidermal growth factor receptor (EGFR) and regulate EGFR signaling in CC HeLa cells. In this study, the effect of EBP50 expression on CC cell proliferation and prognosis of CC patients by regulating EGFR signaling was investigated. We found that EBP50 expression level was significantly downregulated in CC tissues. EBP50 expression negatively correlated with CC cell proliferation, cell cycle and the activation of EGFR-mediated ERK signaling. EBP50 knockdown abolished its inhibition on EGF-induced ERK activation, suggesting EBP50 regulated EGFR signaling. In order to further explore EBP50 regulated EGFR signaling via interaction, we constructed EBP50_DD mutant which disrupted its interaction with EGFR. EBP50_DD overexpression attenuated the inhibition of EBP50_WT on EGFR-mediated ERK signaling, further revealing EBP50 regulated EGFR signaling via its interaction with EGFR. EGFR activation was associated with poor prognosis of CC patients. EBP50 could not predict the prognosis of all CC patients. However, after ruling out patients with egfr/ErbB mutation or copy number variation (CNV) and (chemo)radiation, which caused continuous EGFR activation and affected the prognosis of patients, respectively, EBP50 expression level exhibited the prognosis prediction ability, revealing EBP50 affected prognosis of CC patients via regulating EGFR signaling. In conclusion, EBP50 played an important role in CC cell proliferation and prognosis prediction of CC patients by interacting with EGFR and regulating EGFR signaling. EBP50 might be a potential precise therapeutic target or prognostic marker for CC patients.

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EGFR Promoter Methylation, EGFR Mutation, and HPV Infection in Chinese Cervical Squamous Cell Carcinoma

Cited by 10 publications

References 24 publications

miR-133a inhibits cervical cancer growth by targeting EGFR

miR-133a inhibits cervical cancer growth by targeting EGFR

Effects of Tetrahydrocurcumin on Tumor Growth and Cellular Signaling in Cervical Cancer Xenografts in Nude Mice

EBP50 interacts with EGFR and regulates EGFR signaling to affect the prognosis of cervical cancer patients

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