Decreased p21 Expression in HPV-18 Positive Cervical Carcinomas

Huang, Lee-Wen; Seow, Kok-Min; Lee, Chin-Cheng; Lin, Yu‐Hung; Pan, Hun-Shan; Chen, Heng-Ju

doi:10.1007/s12253-009-9191-8

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…These findings demonstrate that cells expressing HPV18E6 efficiently degraded p53, leading to the inactivation of the p21and the inability to protect against cellular transformation ( 46 ). This finding is consistent with other studies that have shown that p21 gene transcription is inhibited by HPVE6-mediated p53 degradation and that its reduced expression is also observed in invasive squamous cell carcinomas ( 18 , 47 , 48 ).…”

Section: Discussionsupporting

confidence: 93%

Delineation of the HPV11E6 and HPV18E6 Pathways in Initiating Cellular Transformation

2017

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Although high-risk human papillomaviruses (HPVs) are the major risk factors for cervical cancer they have been associated with several other cancers, such as head and neck and oral cancers. Since integration of low-risk HPV11 DNA has been demonstrated in esophageal tumor genomes, this study compared the effects of low-risk HPV11E6 and high-risk HPV18E6 on cellular gene expression. The HPV11E6 and HPV18E6 genes were cloned into an adenoviral vector and expressed in human keratinocytes (HaCaT) in order to investigate early events and to eliminate possible artifacts introduced by selective survival of fast growing cells in stable transfection experiments. HPV11E6 had very little effect on p21 and p53 gene expression, while HPV18E6 resulted in a marked reduction in both these proteins. Both HPV11E6 and HPV18E6 enabled growth of colonies in soft agar, but the level of colony formation was higher in HPV18E6 infected cells. DNA microarray analysis identified significantly differentially regulated genes involved in the cellular transformation signaling pathways. These findings suggest that HPV11E6 and HPV18E6 are important in initiating cellular transformation via deregulation of signaling pathways such as PI3K/AKT and pathways that are directly involved in DNA damage repair, cell survival, and cell proliferation. This study shows that the low-risk HPV11E6 may have similar effects as the high-risk HPV18E6 during the initial stages of infection, but at a much reduced level.

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Section: Discussionsupporting

confidence: 93%

Delineation of the HPV11E6 and HPV18E6 Pathways in Initiating Cellular Transformation

2017

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“…As a sexually transmitted agent, HPV are involved in transformation and maintaining of transformed status ( 47 ). Many studies have reported that HPV can also alter the expression of p21 ( 48 – 50 ). Thus, we searched the GEO dataset to seek for information about the relationship between MNX1 and HPV viral infection.…”

Section: Discussionmentioning

confidence: 99%

MNX1 Promotes Malignant Progression of Cervical Cancer via Repressing the Transcription of p21cip1

Zhu

Zhang

et al. 2020

Front. Oncol.

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Motor neuron and pancreas homeobox 1 (MNX1) is a development-related genes and has been found to be highly expressed in several cancers. However, its biological function in cervical cancer remains largely unexplored. QRT-PCR, western blot, and IHC showed that MNX1 was abnormally overexpressed in cervical cancer tissues and cell lines. The high expression level of MNX1 correlated with poorer clinicopathologic characteristics in cervical cancer patients. Evaluated by RTCA (Real Time Cellular Analysis) proliferation assay, colony formation assay, EdU assay, transwell assay, and matrigel assay, we found that knockdown of MNX1 inhibited proliferation, migration and invasion of cervical cancer in vitro, while overexpression of MNX1 promoted malignant phenotype of cervical cancer. And subcutaneous xenograft model confirmed the malignant phenotype of MNX1 in vivo. Furthermore, flow cytometry, chromatin immunoprecipitation, and luciferase reporter assay indicated that MNX1 accelerated cell cycle transition by transcriptionally downregulating cyclin-dependent kinases p21 cip1. In summary, our study revealed that MNX1 exerted an oncogenic role in cervical cancer via repressing the transcription of p21 cip1 and thus accelerating cell cycle progression. Our results suggested that MNX1 was a potential diagnostic marker and therapeutic target for cervical cancer patients.

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“…On the other hand, p27 was reported to decrease from normal cases to carcinoma (Cheung et al, 2001). On the other hand, Huang et al (2010) reported that p21 expression decreased in HPV 18 positive carcinomas. The fact that aberrant expression of p27, cyclin E and p16 are early events in carcinogenesis (while p21 occur late in cervical carcinogenesis) might be of interest for early diagnostic and for monitoring patients with cervical dysplasia (Bahnassy et al, 2007).…”

Section: Cell Cycle Regulation Markersmentioning

confidence: 99%