MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

Zhou, Hongping; Qian, Lu‐Xi; Zhang, Nan; Gu, Jian; Ding, Kai; Wu, Jing; Lü, Zhiwei; Du, Mengnan; Zhu, Hongming; Wu, Jianzhong; He, Xia; Yin, Li

doi:10.3892/ol.2018.8524

Cited by 3 publications

(3 citation statements)

References 48 publications

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“…Apoptosis is associated with radiosensitivity; increased apoptosis indicates elevated radiosensitivity (48–50). Numerous molecules and pathways are involved in apoptotic processes, including the mitochondria, which serve key roles (51–53).…”

Section: Discussionmentioning

confidence: 99%

Silencing of heat shock protein 27 increases the radiosensitivity of non‑small cell lung carcinoma cells

Xu¹,

Lin²,

Zheng³

et al. 2019

Mol Med Report

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Radiotherapy is a useful treatment for malignant tumors, including lung carcinoma; however, non-small cell lung carcinoma (NSCLC) is frequently insensitive to radiation. It has been reported that heat shock protein 27 (HSPB1) is a radioresistance-associated protein in nasopharyngeal carcinoma. In the present study, the role of HSPB1 in NSCLC cells induced by irradiation was investigated. The viability of cells was determined by a Cell Counting Kit-8 assay. The apoptotic activity, cell cycle distribution and mitochondrial membrane potential (MMP) of cells were evaluated via flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were employed to measure the expression of various genes and proteins. It was observed that knockdown of HSPB1 with small interfering RNA (si-HSPB1) markedly decreased the viability of A549 NSCLC cells and induced cell cycle arrest in the G2/M phase following exposure to 6 Gy irradiation. Furthermore, it was revealed that si-HSPB1 significantly downregulated cyclin B1 and cyclin G1 expression. Additionally, si-HSPB1 promoted apoptosis and depolarized the MMP of cells exposed to 6 Gy irradiation. The expression levels of B-cell lymphoma-2 (Bcl-2), mitochondrial cytochrome c (cyto c ) and pro-caspase-8 were downregulated, whereas those of Bcl-2 associated X protein (Bax), cytosolic cyto c and cleaved-caspase-8 were upregulated. Collectively, silencing of HSPB1 increased the radiosensitivity of NSCLC cells by reducing cell viability, depolarizing the MMP, arresting the cell cycle in the G2/M phase and promoting cell apoptosis. Therefore, HSPB1 may be a novel target for increasing radiosensitivity in the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Silencing of heat shock protein 27 increases the radiosensitivity of non‑small cell lung carcinoma cells

Xu¹,

Lin²,

Zheng³

et al. 2019

Mol Med Report

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“…MIIP was characterized by its role in inhibiting migration and invasion in glioma, and hence the name. Since the identification of MIIP [ 2 ], a limited number of studies addressed the function and mechanism of MIIP in tumorigenesis, with most of them indicate MIIP plays inhibitory effects on tumorigenesis in many types of cancer [ 6 – 9 , 14 , 31 – 34 ]. Besides, a few study also reported opposite effects of MIIP.…”

Section: Discussionmentioning

confidence: 99%

MIIP functions as a novel ligand for ITGB3 to inhibit angiogenesis and tumorigenesis of triple-negative breast cancer

et al. 2022

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Migration and invasion inhibitory protein (MIIP) has been identified as a tumor suppressor in various cancer types. Although MIIP is reported to exert tumor suppressive functions by repressing proliferation and metastasis of cancer cells, the detailed mechanism is poorly understood. In the present study, we found MIIP is a favorable indicator of prognosis in triple-negative breast cancer. MIIP could inhibit tumor angiogenesis, proliferation, and metastasis of triple-negative breast cancer cells in vivo and in vitro. Mechanistically, MIIP directly interacted with ITGB3 and suppressed its downstream signaling. As a result, β-catenin was reduced due to elevated ubiquitin-mediated degradation, leading to downregulated VEGFA production and epithelial mesenchymal transition. More importantly, we found RGD motif is essential for MIIP binding with ITGB3 and executing efficient tumor-suppressing effect. Our findings unravel a novel mechanism by which MIIP suppresses tumorigenesis in triple-negative breast cancer, and MIIP is thus a promising molecular biomarker or therapeutic target for the disease.

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“…There are selected genotypes that promote radiosensitivity and are associated with various clinical conditions. The migration and invasion inhibitory protein gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells [51]. Melanoma cells have been reported to demonstrate a heterogeneous range of radiosensitivity and are radiosensitized by inhibition of proto-oncogene B-RAF [52].…”

Section: Strengths Of Tbddmentioning

confidence: 99%

Drug discovery strategies for acute radiation syndrome

Singh

Seed²,

Olabisi

2019

Expert Opinion on Drug Discovery

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Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach. Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims. Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a 'hybrid' strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS.

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MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

Cited by 3 publications

References 48 publications

Silencing of heat shock protein 27 increases the radiosensitivity of non‑small cell lung carcinoma cells

Silencing of heat shock protein 27 increases the radiosensitivity of non‑small cell lung carcinoma cells

MIIP functions as a novel ligand for ITGB3 to inhibit angiogenesis and tumorigenesis of triple-negative breast cancer

Drug discovery strategies for acute radiation syndrome

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