PEP06 polypeptide 30 exerts antitumour effect in colorectal carcinoma <i>via</i> inhibiting epithelial–mesenchymal transition

Yu, Su Jeong; Li, Linna; Tian, Wei; Nie, Dan; Mu, Wei; Qiu, Fang; Liu, Yu; Liu, Xinghan; Du, Zhenhong; Chu, Wenfeng; Yang, Baofeng

doi:10.1111/bph.14352

Cited by 19 publications

(26 citation statements)

References 63 publications

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“…Among the diagnostic candidates, miR-146b-5p is the most intensively investigated biomarker. Numerous studies have demonstrated that miR-146b can be stably detected in serum or plasma and has the potential to be the novel diagnostic biomarker for diseases other than thyroid cancer (Bookland et al, 2018), while also playing a controversial role in the initiation and development of colorectal cancer, leukemia, and glioma (Li et al, 2013;Zhang et al, 2016;Yu et al, 2018;Jia et al, 2019). In line with the previous publication, plasma exosomal miR-146b-5p, along with another five newly defined miRNA biomarkers, were also eligible for early diagnosis of thyroid nodules in our study.…”

Section: Discussionmentioning

confidence: 99%

A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules

Liang

Tang

et al. 2020

Front. Genet.

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Background: A liquid biopsy using circulating exosomal genetic materials provides new insights for thyroid cancer diagnosis. This study aimed to identify plasma-derived exosomal biomarkers that could be used for early detection of papillary thyroid carcinoma (PTC). Method: Exosomal miRNAs in plasma were isolated from patients with benign thyroid nodules and patients with PTC. Profiling of exosomal miRNA was performed using RNA sequencing (RNA-seq) to identify miRNA candidates and differentiate the benign from malignant. The validation cohort consisted of 30 patients with benign thyroid nodules, 35 PTC patients, and 31 healthy individuals. Real-time PCR was used to quantify the expression of miRNA candidates. The diagnostic potential of the candidates was evaluated by receiver operating characteristic (ROC) curves. Results: After RNA-seq, eight plasma exosomal miRNAs were selected as candidates. Further validation indicated that the levels of exosomal miR-16-2-3p, miR-223-5p, miR-34c-5p, miR-182-5p, miR-223-3p, and miR-146b-5p were significantly lower in nodules compared to healthy controls (p < 0.0001), whereas miR-16-2-3p and miR-223-5p were significantly higher in the PTC cases than in those with benign nodules (p < 0.05). ROC analyses revealed that the above six miRNAs were potent indicators for detection of thyroid nodules. Meanwhile, miR-16-2-3p and miR-223-5p can be utilized for detecting PTC from benign nodules. Additionally, combined miRNA panels showed increased diagnostic sensitivities and specificities compared to single miRNA markers. Conclusion: Six aberrantly expressed plasma exosomal miRNAs may be used as diagnostic biomarkers to differentiate thyroid nodules from healthy individuals. The panel consisting of miR-16-2-3p, miR-223-5p, miR-101-3p, and miR-34c-5p are eligible for discriminating benign from malignant thyroid nodules.

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Section: Discussionmentioning

confidence: 99%

A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules

Liang

Tang

et al. 2020

Front. Genet.

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“…Because this upregulation was observed at the protein level, some of the included proteins might likely be converted to actionable targets for the treatment of mesenchymal CRCs of CMS4. Indeed, previous studies of various colon carcinoma models showed that the suppression of EMT may be achieved by integrin (included in ECM receptor interaction pathway) interaction disruptors [77]. Other ECM receptor interaction pathway proteins (Fig 4) could potentially be good candidates for targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Proteome-transcriptome alignment of molecular portraits achieved by self-contained gene set analysis: Consensus colon cancer subtypes case study

Glazko¹,

Zybailov²,

Emmert‐Streib³

et al. 2019

PLoS ONE

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Gene set analysis (GSA) has become the common methodology for analyzing transcriptomics data. However, self-contained GSA techniques are rarely, if ever, used for proteomics data analysis. Here we present a self-contained proteome level GSA of four consensus molecular subtypes (CMSs) previously established by transcriptome dissection of colon carcinoma specimens. Despite notable difference in structure of proteomics and transcriptomics data, many pathway-wide characteristic features of CMSs found at the mRNA level were reproduced at the protein level. In particular, CMS1 features show heavy involvement of immune system as well as the pathways related to mismatch repair, DNA replication and functioning of proteasome, while CMS4 tumors upregulate complement pathway and proteins participating in epithelial-to-mesenchymal transition (EMT). In addition, protein level GSA yielded a set of novel observations visible at the proteome, but not at the transcriptome level, including possible involvement of major histocompatibility complex II (MHC-II) antigens in the known immunogenicity of CMS1 and a connection between cholesterol trafficking and the regulation of Integrin-linked kinase (ILK) in CMS3. Overall, this study proves utility of self-contained GSA approaches as a critical tool for analyzing proteomics data in general and dissecting protein-level molecular portraits of human tumors in particular.

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“…Desiccated PEP06 was kindly provided by the Department of Pharmacology, Harbin Medical University. For in vitro studies, PEP06 was prepared as described previously and applied at low, medium and high concentrations (50, 100, and 200 μg/mL) 28 . Glucose solution (5%) was used in the vehicle control.…”

Section: Methodsmentioning

confidence: 99%

“…Terminal fusion of RGDRGD hexapeptide to the 1–24 amino acid residues of NH 2 -fragment of endostatin is thought to result in amplified therapeutic potential of PEP06 polypeptide 30 due to direct targeting of cancer-specific cellular processes26, 27. Recently, our colleagues have demonstrated a strong antitumor effect of PEP06 on colorectal cancer mediated through interactions between RGD motifs and α v β 3 integrins in tumor cells 28 . We speculated that PEP06 polypeptide as RGD-derivative from endostatin might possess direct therapeutic efficacy against OSCC in the context of interference with clustered organization of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells

Tuguzbaeva

Yue

Chen

et al. 2019

Acta Pharmaceutica Sinica B

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Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), αv integrin is a crucial mediator of multicellular clustering and collective movement in vitro; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent in vitro. Firstly, we found marked enrichment of αv integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of αv integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed αv integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell–cell contacts contributed to diminished collective migration of OSCC in vitro. Overall, these results suggest that PEP06 polypeptide 30 inhibiting αv integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

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PEP06 polypeptide 30 exerts antitumour effect in colorectal carcinoma via inhibiting epithelial–mesenchymal transition

Abstract: PEP06 is a polypeptide that inhibits the growth and metastasis of colon cancer through its RGD motif binding to integrin αvβ3, thereby down-regulating miR-146b-5p to inhibit EMT in vitro and in vivo. It might have potential as a therapeutic for CRC.

Cited by 19 publications

References 63 publications

A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules

A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules

Proteome-transcriptome alignment of molecular portraits achieved by self-contained gene set analysis: Consensus colon cancer subtypes case study

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells

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