Profiling of transcripts and proteins modulated by the E7 oncogene in the lung tissue of E7-Tg mice by the omics approach

Kim, Eun Jin; Kang, Jeong Woo; Cho, Min-Chul; Lee, So Jung; Seo, Eun-Hee; Choi, Hee-Sook; Kim, Yumi; Kim, Jung-Hee; Kang, Kum Yong; Kim, Kwang Pyo; Han, Jae Yong; Sheen, Yi‐Shuan; Yum, Young Na; Park, Sue-Nie; Yoon, Do‐Young

doi:10.3892/mmr_00000073

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…Results showed downregulation of ALDH1A1 and ALDH3A1 in H1792 cells and Aldh1a1 in MDA-F471 cells, which are known to be overexpressed in KRAS-mutant LUAD CSCs, the downregulation of CCL20 in H1792 and MDA-F471, which plays a major role in the growth and metastasis of lung cancer cells, and the downregulation of Alcam and Tnf in MDA-F471, epithelial cell marker and proinflammatory cytokine, respectively [48]. These findings are consistent with other studies that stated the effects of anti-tumor agents on the CSC population using sphere-forming assay [46][47][48][49][50]57,58]. Furthermore, they motivate further investigations to determine the ability of AlgSulf n to target and affect CSCs growth and the pathway that is affected by the AlgSulf n .…”

Section: Discussionsupporting

confidence: 85%

“…QRT-PCR was performed as per the conditions detailed in Tables S1-S3. In addition, the qRT-PCR preliminary results of the cultivated spheres (n = 1) showed that the increase in the sulfation of biomimetic GAGs led to the decrease in the stemness properties of CSCs by down-regulation of some CSCs' markers ( Figure S5) [49][50][51][52][53][54][55][56]. Results showed downregulation of ALDH1A1 and ALDH3A1 in H1792 cells and Aldh1a1 in MDA-F471 cells, which are known to be overexpressed in KRAS-mutant LUAD CSCs, the downregulation of CCL20 in H1792 and MDA-F471, which plays a major role in the growth and metastasis of lung cancer cells, and the downregulation of Alcam and Tnf in MDA-F471, epithelial cell marker and proinflammatory cytokine, respectively [48].…”

Section: Discussionmentioning

confidence: 99%

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Anti-Tumor Effects of Biomimetic Sulfated Glycosaminoglycans on Lung Adenocarcinoma Cells in 2D and 3D In Vitro Models

et al. 2020

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Lung cancer development relies on cell proliferation and migration, which in turn requires interaction with extracellular matrix (ECM) components such as glycosaminoglycans (GAGs). The mechanisms through which GAGs regulate cancer cell functions are not fully understood but they are, in part, mediated by controlled interactions with cytokines and growth factors (GFs). In order to mechanistically understand the effect of the degree of sulfation (DS) of GAGs on lung adenocarcinoma (LUAD) cells, we synthesized sulfated alginate (AlgSulf) as sulfated GAG mimics with DS = 0.0, 0.8, 2.0, and 2.7. Human (H1792) and mouse (MDA-F471) LUAD cell lines were treated with AlgSulf of various DSs at two concentrations 10 and 100 µg/mL and their anti-tumor properties were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion, and wound healing assays for 2D models and sphere formation assay for the 3D model. The proliferation and number of live MDA-F471 cells at the concentration of 100 µg/mL decreased significantly with the increase in the DS of biomimetic GAGs. In addition, the increase in the DS of biomimetic GAGs decreased cell migration (p < 0.001 for DS = 2.0 and 2.7 compared to control) and decreased the diameter and number of spheres formed (p < 0.001). The increased DS of biomimetic GAGs attenuated the expression of cancer stem cell (CSC)/progenitor markers in the 3D cultures. In conclusion, GAG-mimetic AlgSulf with increased DS exhibit enhanced anti-proliferative and migratory properties while also reducing growth of KRAS-mutant LUAD spheres in vitro. We suggest that these anti-tumor effects by GAG-mimetic AlgSulf are possibly due to differential binding to GFs and consequential decreased cell stemness. AlgSulf may be suitable for applications in cancer therapy after further in vivo validation.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Anti-Tumor Effects of Biomimetic Sulfated Glycosaminoglycans on Lung Adenocarcinoma Cells in 2D and 3D In Vitro Models

et al. 2020

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Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional Profiling of E7-Expressing Cells

Yang

Zhang

Gao

et al. 2016

J Virol

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The E7 oncoprotein of the high-risk human papillomavirus (HPV) plays a major role in HPV-induced carcinogenesis. E7 abrogates the G 1 cell cycle checkpoint and induces genomic instability, but the mechanism is not fully understood. In this study, we performed RNA sequencing (RNA-seq) to characterize the transcriptional profile of keratinocytes expressing HPV 16 (HPV-16) E7. At the transcriptome level, 236 genes were differentially expressed between E7 and vector control cells. A subset of the differentially expressed genes, most of them novel to E7-expressing cells, was further confirmed by real-time PCR. Of interest, the activities of multiple transcription factors were altered in E7-expressing cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were investigated. The upregulated genes were enriched in cell cycle and DNA replication, as well as in the DNA metabolic process, transcription, DNA damage, DNA repair, and nucleotide metabolism. Specifically, we focused our studies on the gene encoding WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein), one of the genes that was upregulated in E7-expressing cells. WDHD1 is a component of the replisome that regulates DNA replication. Recent studies suggest that WDHD1 may also function as a DNA replication initiation factor as well as a G 1 checkpoint regulator. We found that in E7-expressing cells, the steady-state level of WDHD1 protein was increased along with the half-life. Moreover, downregulation of WDHD1 reduced E7-induced G 1 checkpoint abrogation and rereplication, demonstrating a novel function for WDHD1. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. IMPORTANCEThe high-risk HPV types induce cervical cancer and encode an E7 oncoprotein that plays a major role in HPV-induced carcinogenesis. However, the mechanism by which E7 induces carcinogenesis is not fully understood; specific anti-HPV agents are not available. In this study, we performed RNA-seq to characterize transcriptional profiling of keratinocytes expressing HPV-16 E7 and identified more than 200 genes that were differentially expressed between E7 and vector control cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were identified. Significantly, the WDHD1 gene, one of the genes that is upregulated in E7-expressing cells, was found to play an important role in E7-induced G 1 checkpoint abrogation and rereplication. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. H uman papillomaviruses (HPVs) are small DNA viruses that replicate in squamous epithelia. Specific types of HPV (highrisk HPVs) are the causative agents for cervical and several other cancers (1). The transforming properties of high-risk HPVs such as HPV 16 (HPV-16) primarily depend on E7 as well as E6 oncogenes (1, 2). HPV E6 and E7 proteins promote the degradation of p53 and pRb, respectively (3, 4). E7 from the high-risk...

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Profiling of transcripts and proteins modulated by the E7 oncogene in the lung tissue of E7-Tg mice by the omics approach

Cited by 2 publications

References 14 publications

Anti-Tumor Effects of Biomimetic Sulfated Glycosaminoglycans on Lung Adenocarcinoma Cells in 2D and 3D In Vitro Models

Anti-Tumor Effects of Biomimetic Sulfated Glycosaminoglycans on Lung Adenocarcinoma Cells in 2D and 3D In Vitro Models

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional Profiling of E7-Expressing Cells

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