Biology of PEST‐Containing Nuclear Protein: A Potential Molecular Target for Cancer Research

Khan, Nazeer Hussain; Chen, Hao-Jie; Fan, Yu; Surfaraz, Muhammad; Ahammad, MD.Faysal; Qin, Yang-Zhe; Shahid, M. Khan; Virk, Razia; Wu, Dongdong; Ji, Xin‐Ying

doi:10.3389/fonc.2022.784597

Cited by 4 publications

(3 citation statements)

References 58 publications

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“…PCNP is involved in cell cycle regulation, and high levels of PCNP have been found in various cancer cell lines, including U-937 myeloid leukemia cells and HepG2 hepatocellular carcinoma cells, suggesting that PCNP may be engaged in carcinogenesis ( 27 ). However, PCNP’s role and mode of action in OSCC remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Tissue mechanics modulate PCNP expression in oral squamous cell carcinomas with different differentiation

Zhang

Guo²,

Shen³

et al. 2023

Front. Oncol.

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BackgroundPEST-containing nuclear protein (PCNP), a novel zinc finger protein, participates in cell cycle regulation. Previous studies have confirmed that PCNP plays a role in mediating cellular development and invasion in a variety of cancer types. However, the relationship between PCNP expression and the occurrence and development of oral squamous cell carcinoma (OSCC) requires further exploration. In this study, we used biological atomic force microscopy to examine the histomorphological and mechanical properties of OSCC to explore the relationship between PCNP expression and differentiation of OSCC.MethodsSeventy-seven OSCC samples with varying degrees of differentiation were selected for hematoxylin and eosin staining, immunohistochemistry, and cellular mechanical measurement. The expression of PCNP and the mechanical properties such as stiffness and roughness of the tissue interface in OSCC samples were investigated. The Kaplan-Meier survival curve was utilized to assess the relationship of PCNP expression with patient survival.ResultsThe level of PCNP was significantly higher in well-differentiated OSCC than in moderately and poorly differentiated OSCC (P < 0.001). High expression of PCNP was specifically associated with higher tumor differentiation, lack of lymph node metastasis, and lower tumor node metastasis stage (all P < 0.05). Patients with high PCNP expression had a higher survival rate than those with low PCNP expression. The average variation of stiffness within a single tissue ranged from 347 kPa to 539 kPa. The mean surface roughness of highly, moderately, and poorly differentiated OSCC and paraneoplastic tissues were 795.53 ± 47.2 nm, 598.37 ± 45.76 nm, 410.16 ± 38.44 nm, and 1010.94 ± 119.07 nm, respectively. Pearson correlation coefficient demonstrated a positive correlation between PCNP expression and tissue stiffness of OSCC (R = 0.86, P < 0.001).ConclusionThe expression of PCNP was positively correlated with patient survival, tumor differentiation, and mechanical properties of tissue interfaces. PCNP is a potential biomarker for the early diagnosis and staging of OSCC. Furthermore, determination of the mechanical properties of the tissue interface could provide further useful information required for the detection and differentiation of OSCC.

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Section: Discussionmentioning

confidence: 99%

Tissue mechanics modulate PCNP expression in oral squamous cell carcinomas with different differentiation

Zhang

Guo²,

Shen³

et al. 2023

Front. Oncol.

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“…PCNP with the presence of high-score PEST sequences and potential phosphorylation sites is reminiscent of key molecule governing cell-cycle progression and transcriptional regulation. Moreover, transcription patterning analysis of a PCNP showed that it is co-expressed with MARCH7, BMI1, TMEM123, TRAM1, and PSMC6 39 . Whereas, in searching for PCNP-associating direct targets, ChIP or ChIP-seq experiment should be conducted for validation.…”

Section: Discussionmentioning

confidence: 99%

PCNP is a novel regulator of proliferation, migration, and invasion in human thyroid cancer

Chen¹,

Liu²,

Hong³

et al. 2022

Int. J. Biol. Sci.

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Thyroid cancer (TC) has increased globally, with a prominent increase in small, papillary thyroid cancers. PEST-containing nuclear protein (PCNP), a nuclear protein, has been found to be associated with human cancers in recent years. However, the role and molecular mechanism of PCNP in thyroid cancer remain underexplored. In the present study, the results showed that the expression levels of PCNP in human thyroid tissues were higher than those in adjacent non-tumor tissues. Overexpression of PCNP reduced the proliferation, migration, and invasion of human thyroid cancer cells and down-regulation of PCNP showed reverse effects. In addition, PCNP regulated cell cycle arrest through modifications in the expression of cell cycle regulating genes and PCNP affected apoptosis via activation of ERK/JNK/p38 pathway in thyroid cancer cells. Moreover, PCNP overexpression promoted autophagy by reducing the expression levels of Wnt/β-catenin pathway in TC cells, however, PCNP knockdown had opposite effects. Furthermore, PCNP overexpression reduced the growth of xenografted human thyroid cancer, whereas PCNP knockdown showed opposite trends. In conclusion, in vitro and in vivo data demonstrate that PCNP as a tumor suppressor gene may serve as a novel prognostic and potential therapeutic marker in human thyroid cancer.

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“…Bioinformatics study of PCNP congenital disorders [49] . PTMs refer to amino acid side chain modifications in some proteins after their biosynthesis.…”

Section: Gene and Protein In Diseasementioning

confidence: 99%

Structural, functional, phylogenetic, and molecular dynamic simulation study of PEST-containing nuclear protein: An e-science view

Khan¹,

Shahid²,

Wang³

et al. 2022

GPD

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PEST-containing nuclear protein (PCNP) is a short-lived novel nuclear protein. It has been well evaluated that PCNP mediates the progression of several cancers, but the exact mechanisms are still under investigation. In this study, we provided an e-science view of PCNP protein from the aspects of protein structure, interactions, and bioinformatics-based analysis related to evolutionary features as well as proteomic profile. The phylogenetic relationship results reveal that PCNP is closely related to Pan troglodytes and the Bovidae family, while being distantly related to the Muridae family. The analysis of the physicochemical properties of PCNP demonstrated that it is a thermolabile protein which is slightly acidic and hydrophilic in nature. Further, coexpression and protein-protein interaction analyses were carried out, which demonstrated that the PCNP gene was remarkably expressed with MORF4LI and RSL24D1 genes and has close interactions with TRAM1, PSMC6, SRP9, PRKRIR, UHRF2, and BMI1 proteins. Gene ontology and pathway enrichment analyses showed that PCNP has a high tendency to work in cell cycle regulation. Moreover, among the four 3D structure generating tools, I-TASSER-generated structure had the highest quality factor score. The validation analysis revealed that the I-TASSER-generated structure exhibited the best quality factor score with maximum amino acids in the favored region. In addition, molecular dynamic simulation analysis approved the stable structure of the PCNP. This is the first study that highlights the usefulness of the understanding of the structural and functional analysis of the PCNP, which lays the groundwork for further experimental studies to validate the outcome.

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Biology of PEST‐Containing Nuclear Protein: A Potential Molecular Target for Cancer Research

Cited by 4 publications

References 58 publications

Tissue mechanics modulate PCNP expression in oral squamous cell carcinomas with different differentiation

Tissue mechanics modulate PCNP expression in oral squamous cell carcinomas with different differentiation

PCNP is a novel regulator of proliferation, migration, and invasion in human thyroid cancer

Structural, functional, phylogenetic, and molecular dynamic simulation study of PEST-containing nuclear protein: An e-science view

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