Tumor-suppressive p53 Signaling Empowers Metastatic Inhibitor KLF17-dependent Transcription to Overcome Tumorigenesis in Non-small Cell Lung Cancer

Ali, Amjad; Bhatti, Muhammad Zeeshan; Shah, Abdus Saboor; Duong, Hong‐Quan; Alkreathy, Huda M.; Mohammad, Shah Faisal; Khan, Rahmat Ali; Ahmad, Ayaz

doi:10.1074/jbc.m114.635730

Cited by 21 publications

(16 citation statements)

References 49 publications

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“…With the advances of oncological researches, many critical oncogenes or tumor suppressors in NSCLC were identified, such as p53, EGFR, PD-1/ PD-L1 [29][30][31]. Several molecular targeted therapies have been developed, such as EGFR-tyrosine kinase inhibitor and PD-1/PD-L1 antibodies [32,33].…”

Section: Discussionmentioning

confidence: 99%

High Expression of Long Noncoding RNA PCNA-AS1 Promotes Non-Small-Cell Lung Cancer Cell Proliferation and Oncogenic Activity via Upregulating CCND1

Wu¹,

Zhu²,

Xia³

et al. 2020

J. Cancer

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Accumulating evidences showed that aberrantly expressed long noncoding RNAs (lncRNAs) have critical roles in many cancers. However, the expression and roles of a poorly studied lncRNA PCNA-AS1 in non-small-cell lung cancer (NSCLC) remain unknown. In this study, we investigated the expression, clinical significance, biological roles, and functional mechanism of PCNA-AS1 in NSCLC. Our results showed that PCNA-AS1 was upregulated in NSCLC tissues and cell lines, and correlated with TNM stages. Functional experiments showed that overexpression of PCNA-AS1 promoted NSCLC cell proliferation and cell cycle progression. Depletion of PCNA-AS1 inhibited NSCLC cell proliferation and cell cycle progression, and also inhibited NSCLC tumor growth in vivo. Mechanistically, we found that PCNA-AS1 upregulated CCND1 expression. The expression of PCNA-AS1 was positively correlated with that of CCND1 in NSCLC tissues. Moreover, depletion of CCND1 abrogated the oncogenic roles of PCNA-AS1 in NSCLC. In conclusion, highly expressed PCNA-AS1 promotes NSCLC cell proliferation and oncogenic activity via upregulating CCND1. Our results imply that PCNA-AS1 might serve as a therapeutic target for NSCLC.

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Section: Discussionmentioning

confidence: 99%

High Expression of Long Noncoding RNA PCNA-AS1 Promotes Non-Small-Cell Lung Cancer Cell Proliferation and Oncogenic Activity via Upregulating CCND1

Wu¹,

Zhu²,

Xia³

et al. 2020

J. Cancer

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Section: Krüppel-like Factor 17mentioning

confidence: 97%

“…These studies suggested that p53 recruits p300 to the KLF17 promoter to acetylate and turn on transcription [177]. In addition, p53 also physically interacts with KLF17 and promotes binding of KLF17 to certain gene promoters and promotes transcription of p53, p21, and pRB [177]. These data suggest an intricate cross-talk between KLF17 and p53 in tumorigenesis.…”

Section: Krüppel-like Factor 17mentioning

confidence: 97%

“…Further evidence in non-small-cell lung cancer also suggests that KLF17 could function as a tumor suppressor [177]. These studies suggested that p53 recruits p300 to the KLF17 promoter to acetylate and turn on transcription [177]. In addition, p53 also physically interacts with KLF17 and promotes binding of KLF17 to certain gene promoters and promotes transcription of p53, p21, and pRB [177].…”

Section: Krüppel-like Factor 17mentioning

confidence: 99%

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Transcriptional and Epigenetic Regulation of Krüppel-Like Transcription Factors

Salmon¹

2020

Gene Expression and Phenotypic Traits

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Krüppel-like factors (KLFs) are a family of zinc finger transcription factors (ZF-TF) that are now known to be involved in complex biological processes including cancer, proliferation, and cardiovascular disease as well as developmental processes. KLFs first gained notoriety when it became known that they are crucial for promoting and maintenance of stem cell pluripotency. Over the past 20 years since the discovery of Krüppel-like factor 1 (KLF1), this transcription factor family has grown to include 18 members and 7 closely related members of the specificity protein 1 (Sp1) family. In the present study, we review the mechanisms related to regulation of KLFs by direct promoter activation or repression. We will also review and discuss some mechanisms of posttranslational modifications that could affect KLF function. We seek to understand how these transcriptional regulators are themselves regulated and how that regulation could become aberrant during various disease processes.

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“…Krüppel-like factors are highly conserved zinc finger transcription factors that serve as key regulators of critical biological cellular processes, including cell proliferation, differentiation, apoptosis, and migration [9,10]. Many studies that have focused on the function of KLF17 in tumorigenesis have reported that KLF17 plays a vital role in cancer development [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of KLF17 Predicts a Favorable Prognosis in Patients with Oral Squamous Cell Carcinoma: A Retrospective Study

et al. 2020

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Background and Objectives: Patients with oral squamous cell carcinoma (OSCC), a common malignancy in Asian countries, have a poor prognosis. We investigated the role of Krüppel-like factor 17 (KLF17) and its prognostic significance in OSCC. Materials and Methods: KLF17 expression was measured by immunohistochemical staining of specimens from 283 patients with OSCC. We analyzed correlations between KLF17 expression and clinicopathologic features and between KLF17 expression and overall survival. The prognostic value of KLF17 was tested using Kaplan–Meier analysis and Cox proportional hazard models. Results: Among the 283 patients, high KLF17 expression was significantly associated with an early OSCC stage and low T-value (p = 0.033 and p = 0.036, respectively). The five-year survival rates were better in patients with high KLF17 expression than with low expression (66.5% and 49.6%, respectively). The prognostic role of KLF17 was further confirmed through multivariate analysis (hazard ratio 1.506, 95% confidence interval 1.034–2.191, p = 0.033). The prognostic value was more significant in patients with a history of betel quid chewing or with a low T-value. Conclusions: High KLF17 expression can serve as a marker for a favorable prognosis in patients with OSCC. The prognostic role of KLF17 is more significant in patients with a history of betel quid chewing or a low T-value.

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Tumor-suppressive p53 Signaling Empowers Metastatic Inhibitor KLF17-dependent Transcription to Overcome Tumorigenesis in Non-small Cell Lung Cancer

Cited by 21 publications

References 49 publications

High Expression of Long Noncoding RNA PCNA-AS1 Promotes Non-Small-Cell Lung Cancer Cell Proliferation and Oncogenic Activity via Upregulating CCND1

High Expression of Long Noncoding RNA PCNA-AS1 Promotes Non-Small-Cell Lung Cancer Cell Proliferation and Oncogenic Activity via Upregulating CCND1

Transcriptional and Epigenetic Regulation of Krüppel-Like Transcription Factors

Overexpression of KLF17 Predicts a Favorable Prognosis in Patients with Oral Squamous Cell Carcinoma: A Retrospective Study

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