Neuropilin 1 expression correlates with the Radio‐resistance of human non‐small‐cell lung cancer cells

Dong, Juan; Gao, Hui; Zuo, Si Yao; Zhang, Hai Qin; Zhang, Gang; Sun, Shilong; Han, Hai Ling; Jin, Lin; Li, Shao; Wei, Wei; Jin, Song

doi:10.1111/jcmm.12623

Cited by 34 publications

(31 citation statements)

References 40 publications

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“…NRP1 can bind many ligands and various types of coreceptors, such as vascular endothelial growth factor and semaphorin family members 27,28. Through the mediation of several different signaling pathways, NRP1 is involved in the regulation of cell survival and motility 29,30. Recently, Lu et al31 reported that NRP1 was significantly upregulated in primary and metastatic MM compared with common nevi and dysplas-tic nevi.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

Xu¹,

Chen²,

He³

et al. 2016

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MicroRNAs (miRs) are a class of small noncoding RNAs that negatively regulate the gene expression by directly binding to the 3′ untranslated region of their target mRNA, thus resulting in mRNA degradation or translational repression. miR-9 has recently been demonstrated to play a role in the development and progression of malignant melanoma (MM), but the regulatory mechanism of miR-9 in the malignant phenotypes of MM still remains largely unknown. In this study, a total of 73 pairs of MM tissues and adjacent normal tissues were collected. Real-time reverse transcription polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of miR-9. MTT assay, wound healing assay, and transwell assay were conducted to determine the cell proliferation, migration, and invasion. Luciferase reporter assay was used to determine the targeting relationship between miR-9 and NRP1. Our data demonstrated that miR-9 expression was significantly downregulated in MM tissues compared with that in adjacent normal tissues. The decreased miR-9 level was significantly associated with the tumor stage and metastasis of MM. We also found that the expression level of miR-9 was decreased in MM cell lines (G361, B16, A375, and HME1) compared with normal skin HACAT cells. Ectopic expression of miR-9 led to a significant decrease in the ability of proliferation, migration, and invasion in A375 cells. NRP1 was further identified as a direct target gene of miR-9, and the protein expression of NRP1 was negatively regulated by miR-9 in A375 cells. Furthermore, overexpression of NRP1 reversed the suppressive effects of miR-9 on the malignant phenotypes of A375 cells. In vivo study revealed that miR-9 overexpression decreased the tumor growth, while overexpression of NRP1 increased MM growth. In summary, our findings suggest that the miR-9/NRP1 axis may serve as a potential target for the treatment of MM.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

Xu¹,

Chen²,

He³

et al. 2016

OTT

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“…The survival rate was calculated as the plating efficiency of the irradiated samples relative to that of the sham-irradiated sample. 28 For the cell lines A549 and A549/X, each radiation dose sample was duplicated three times. A multitarget click model of SigmaPlot 12.5 (Systat Software, Inc., San Jose, CA) was used to fit cell survival curves.…”

Section: Colony Formation Assaymentioning

confidence: 99%

Combined Radiotherapy and Anti–PD-L1 Antibody Synergistically Enhances Antitumor Effect in Non–Small Cell Lung Cancer

Gong

Jiang

et al. 2017

Journal of Thoracic Oncology

231

189

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“…Radiotherapy has been applied to treat advanced non-small-cell lung cancer (NSCLC) for the past two decades. However, one major obstacle to successful radiotherapy is the existence of radio-resistance (2). Tyrosine kinase inhibitors can improve the survival of patients with radio-resistant lung adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

Insulin‑like growth factor‑1 receptor knockdown enhances radiosensitivity via the HIF‑1α pathway and attenuates ATM/H2AX/53BP1 DNA repair activation in human lung squamous carcinoma cells

Liu

Chen

et al. 2018

Oncol Lett

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Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor involved in cell proliferation and apoptosis, which is highly expressed in lung squamous cell carcinoma (SCC). The present study aimed to observe the influence of IGF-1R silencing on the radiosensitivity of SCC and investigate the potential mechanisms involved. Human lung SCC H520 cells with relatively high expression of IGF-1R were used. IGF-1R expression was silenced using short hairpin RNA. The influence of IGF-1R silencing on radiosensitivity and apoptosis was assessed using a clone formation assay and flow cytometry. The expression levels of proteins relevant in DNA damage repair and hypoxic signaling pathways were analyzed using western blotting. Decreased expression of IGF-1R led to an increase in the sensitivity of H520 cells to irradiation. Molecular analysis showed that the reduced expression of IGF-1R decreased the protein expression of ataxia-telangiectasia mutated (ATM), H2A histone family member X (H2AX) and p53 binding protein 1 (53BP1), which are associated with the DNA repair pathway. Furthermore, 53BP1 is also known to be involved in apoptosis. Proteins involved in the hypoxic pathway, including hypoxia inducible factor 1 α (HIF-1α), matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor A (VEGFA) were also involved in the radiosensitivity. In conclusion, decreased expression of IGF-1R leads to improved radiosensitivity of SCC cells, and the underlying mechanism may be associated with the decreased expression of proteins involved in ATM/H2AX/53BP1 DNA damage repair and the HIF-1α/MMP-9 hypoxic pathway, which results in the induction of apoptosis and increased radiosensitivity. These findings suggest that targeting of IGF-1R may represent a novel approach for lung SCC radiation treatment.

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Neuropilin 1 expression correlates with the Radio‐resistance of human non‐small‐cell lung cancer cells

Cited by 34 publications

References 40 publications

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

Combined Radiotherapy and Anti–PD-L1 Antibody Synergistically Enhances Antitumor Effect in Non–Small Cell Lung Cancer

Insulin‑like growth factor‑1 receptor knockdown enhances radiosensitivity via the HIF‑1α pathway and attenuates ATM/H2AX/53BP1 DNA repair activation in human lung squamous carcinoma cells

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