POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma

Shinmura, Kazuya; Kato, Hisami; Kawanishi, Yuichi; Yoshimura, Katsuhiro; Tsuchiya, Kazuo; Takahara, Yoshiyuki; Hosokawa, Seiji; Kawase, Akikazu; Sugimura, Haruhiko

doi:10.3390/cancers11050722

Cited by 24 publications

(24 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[22][23][24] In recent studies, PLK4 expression was shown to be significantly higher in malignant versus normal lungs and conferred an unfavourable survival rate, while PLK4 inhibition produces polyploidy and apoptotic death of lung cancers. 25,26 All of these results support our hypothesis that PLK4 may be a downstream target of miR-654-3p. In our study, we observed that PLK4 expression was upregulated in NSCLC tissues compared with the adjacent tissue and was negatively correlated with miR-654-3p in NSCLC patients.…”

Section: Discussionsupporting

confidence: 82%

<p>MiR-654-3p Suppresses Non-Small Cell Lung Cancer Tumourigenesis by Inhibiting PLK4</p>

Pu¹,

Zhang²,

Zhang³

et al. 2020

OTT

View full text Add to dashboard Cite

MiR-654-3p plays important roles in many types of malignant tumours. However, the biological function of miR-654-3p in non-small cell lung cancer (NSCLC) remains unknown. In this study, the role of miR-654-3p in NSCLC was investigated. Methods: qRT-PCR was used to evaluate the level of miR-654-3p in NSCLC tissues and cell lines, while Cell Counting Kit-8, Annexin V/propidium iodide dual staining or TUNEL staining were used to investigate proliferation and apoptosis of NSCLC cells. Luciferase assays and Western blotting were performed to validate potential targets of miR-654-3p. Results: MiR-654-3p levels were significantly decreased in NSCLC patients and cell lines and were significantly correlated with the tumour size and tumour node metastasis stage of NSCLC patients. In A549 cells, miR-654-3p overexpression significantly increased apoptosis and inhibited growth both in vivo and in vitro, while downregulation of miR-654-3p had the opposite effects. In addition, polo-like kinase 4 (PLK4) was shown to be a target gene of miR-654-3p that is negatively regulated by miR-654-3p in A549 cells. Furthermore, PLK4 was observed to be highly expressed in NSCLC tissues and cells, and PLK4 overexpression abolished the inhibitory effects of miR-654-3p overexpression on NSCLC cell proliferation. Finally, the animal experiment results further demonstrated that miR-654-3p inhibits tumour growth and regulates PLK4 expression. Conclusion: Our results demonstrate that miR-654-3p functions as a growth-suppressing miRNA by targeting PLK4 in NSCLC.

show abstract

Section: Discussionsupporting

confidence: 82%

<p>MiR-654-3p Suppresses Non-Small Cell Lung Cancer Tumourigenesis by Inhibiting PLK4</p>

Pu¹,

Zhang²,

Zhang³

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…DNA polymerase θ (POLQ)) in tumors that induce poor OS of patients. 36,37 In contrast, in stomach cancer and colorectal cancer patients, high NEIL3 expression was associated with better cancer-specific survival. Therefore, NEIL3 overexpression may play a very different role in cancers arising from different tissues, as other studies have shown.…”

Section: Discussionmentioning

confidence: 96%

Overexpression ofNEIL3associated with altered genome and poor survival in selected types of human cancer

et al. 2020

View full text Add to dashboard Cite

Base excision repair, which is initiated by the DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cellular outcomes to chemotherapy and carcinogenesis. Endonuclease VIII-like 3 (NEIL3) is a DNA glycosylase protein that is involved in oxidative and interstrand crosslink DNA damage repair. Our previous work has showed that NEIL3 is required to maintain replication fork integrity. It is unknown whether NEIL3 overexpression could contribute to cancer phenotypes, and its prognostic value and use as potential drug target remain unexplored. Our analysis of cancer genomics data sets reveals that NEIL3 frequently undergoes overexpression in several cancers. Furthermore, patients who exhibited NEIL3 overexpression with pancreatic adenocarcinoma, lung adenocarcinoma, lower grade glioma, kidney renal clear cell carcinoma, and kidney papillary cell carcinoma had worse overall survival. Importantly, NEIL3 overexpressed tumors accumulate mutation and chromosomal variations. Furthermore, NEIL3 overexpressed tumors exhibit simultaneous overexpression of homologous recombination genes (BRCA1/2) and mismatch repair genes ( MSH2/MSH6). However, NEIL3 overexpression is negatively correlated with tumor overexpressing nucleotide excision repair genes ( XPA, XPC, ERCC1/ 2). Our results suggest that NEIL3 might be a potential prognosis marker for high-risk patients, and/or an attractive therapeutic target for selected cancers.

show abstract

“…DNA Polymerase Theta (POLQ) is a DNA polymerase involved in translation DNA synthesis (TLS) and DNA doublestrand break (DSB) repair. Moreover, elevated expression levels of Plk4 were largely correlated with overexpression of DNA polymerase PQLQ at both mRNA and protein in LAC and coexpression of Plk4 and POLQ induced more significant centriole overduplication than the expression of either one alone, suggesting the potential cooperation of Plk4 and PQLQ in LAC oncogenesis (208).…”

Section: Plk4 and Lung Cancermentioning

confidence: 94%

Polo-Like Kinase 4’s Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy

et al. 2021

View full text Add to dashboard Cite

Polo-like kinases (Plks) are critical regulatory molecules during the cell cycle process. This family has five members: Plk1, 2, 3, 4, and 5. Plk4 has been identified as a master regulator of centriole replication, and its aberrant expression is closely associated with cancer development. In this review, we depict the DNA, mRNA, and protein structure of Plk4, and the regulation of Plk4 at a molecular level. Then we list the downstream targets of Plk4 and the hallmarks of cancer associated with these targets. The role of Plk4 in different cancers is also summarized. Finally, we review the inhibitors that target Plk4 in the hope of discovering effective anticancer drugs. From authors’ perspective, Plk4 might represent a valuable tumor biomarker and critical target for cancer diagnosis and therapy.

show abstract

POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma

Cited by 24 publications

References 59 publications

<p>MiR-654-3p Suppresses Non-Small Cell Lung Cancer Tumourigenesis by Inhibiting PLK4</p>

<p>MiR-654-3p Suppresses Non-Small Cell Lung Cancer Tumourigenesis by Inhibiting PLK4</p>

Overexpression ofNEIL3associated with altered genome and poor survival in selected types of human cancer

Polo-Like Kinase 4’s Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy

Contact Info

Product

Resources

About