Integrative Bioinformatics Analysis Reveals miR-524-5p/MEF2C Regulates Bone Metastasis in Prostate Cancer and Breast Cancer

Abstract Background Bone metastases are high prevalence in advanced prostate cancer and breast cancer patients, which have a serious impact on the quality of life and survival time of patients. Abnormal expression of microRNAs (miRNAs) has been reported in different types of cancer and metastasis. However, the underlying miRNAs associated with prostate and breast cancer bone metastasis remains unknown. Methods We performed bioinformatics analysis for TCGA cohort to identify differentially expressed miRNAs (DE-miRNAs) and their targets in the metastatic process. Results QPCR confirmed that miR-524-5p expression was down-regulated in prostate and breast cancer cell. And miR-524-5p over-expression restrained cell proliferation, invasion and metastasis ability in prostate and breast cancer. Meanwhile, miR-524-5p specifically targeting MEF2C was verified by luciferase assay. Conclusions In conclusion, our data strongly suggests down-regulation of miR-524-5p appears as a precocious event in prostate and breast cancer, and MEF2C emerges as a new player in prostate and breast cancer bone metastasis.

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Lesion-Based Bone Metastasis Detection in Chest Bone Scintigraphy Images of Prostate Cancer Patients Using Pre-Train, Negative Mining, and Deep Learning

Diagnostics ◽

10.3390/diagnostics11030518 ◽

2021 ◽

Vol 11 (3) ◽

pp. 518

Author(s):

Da-Chuan Cheng ◽

Te-Chun Hsieh ◽

Kuo-Yang Yen ◽

Chia-Hung Kao

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Deep Learning ◽

Bone Metastasis ◽

Cancer Patients ◽

Bone Scintigraphy ◽

Breast Cancer Patients ◽

Location Detection ◽

The Mean ◽

Mean Sensitivity

This study aimed to explore efficient ways to diagnose bone metastasis early using bone scintigraphy images through negative mining, pre-training, the convolutional neural network, and deep learning. We studied 205 prostate cancer patients and 371 breast cancer patients and used bone scintigraphy data from breast cancer patients to pre-train a YOLO v4 with a false-positive reduction strategy. With the pre-trained model, transferred learning was applied to prostate cancer patients to build a model to detect and identify metastasis locations using bone scintigraphy. Ten-fold cross validation was conducted. The mean sensitivity and precision rates for bone metastasis location detection and classification (lesion-based) in the chests of prostate patients were 0.72 ± 0.04 and 0.90 ± 0.04, respectively. The mean sensitivity and specificity rates for bone metastasis classification (patient-based) in the chests of prostate patients were 0.94 ± 0.09 and 0.92 ± 0.09, respectively. The developed system has the potential to provide pre-diagnostic reports to aid in physicians’ final decisions.

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PTHrP(12-48) for the diagnosis of breast cancer bone metastasis.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21039 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21039-e21039

Author(s):

Charity L. Washam ◽

Stephanie D. Byrum ◽

Kim Leitzel ◽

Ali M. Suhail ◽

Allan Lipton ◽

...

Keyword(s):

Breast Cancer ◽

Logistic Regression ◽

Bone Metastasis ◽

Bone Metastases ◽

Cancer Patients ◽

Statistical Significance ◽

Breast Cancer Patients ◽

Parathyroid Hormone Related Protein ◽

Increased Risk ◽

Breast Cancer Bone Metastasis

e21039 Background: Bone metastasis of breast cancer significantly compromises patient morbidity and mortality. Currently, no reliable methods detect or predict patients at increased risk for developing bone metastasis. We utilized 3 independent cohorts of breast cancer patients to validate a highly discriminatory plasma-based proteomic profile that identifies breast cancer bone metastasis. The identity of the most discriminatory protein component identified was a parathyroid hormone-related protein fragment, PTHrP(12-48). Methods: Plasma samples collected from 21 breast cancer patients with clinical evidence of a bone metastasis and 21 patients with no evidence of bone metastasis from time of diagnosis to clinical outcome were evaluated. A novel mass spectrometry-based assay using human serum spiked with synthetic PTHrP(12-48) was used to measure PTHrP(12-48) concentrations (pg/μl). Statistical significance was assessed by one-way ANOVA. ROC curves evaluated the diagnostic potential of PTHrP(12-48) and a simple logistic regression derived from the combined measurement of PTHrP(12-48) and NTx. Results: PTHrP(12-48) concentrations ranged between 11.6 and 92.1 pg/μl in bone metastasis patients and between 4.5 and 34.2 pg/μl in patients without bone metastases. PTHrP(12-48) was significantly increased in bone metastasis plasma (p < 0.05). No significant correlation was identified between PTHrP(12-48) and NTx. ROC analysis of PTHrP(12-48), threshold 18 pg/μl, classified the two groups with high accuracy. Class prediction by the PTHrP(12-48)/NTx logistic regression model increased diagnostic specificity. Conclusions: The measurement of PTHrP(12-48) in patient plasma has potential as a viable clinical measure of bone metastasis. In combination with serum NTx, PTHrP(12-48) may assist in identifying bone metastases in patients presenting with low to normal bone turnover markers.

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Knockdown of AKT3 Activates HER2 and DDR Kinases in Bone-Seeking Breast Cancer Cells, Promotes Metastasis In Vivo and Attenuates the TGFβ/CTGF Axis

Cells ◽

10.3390/cells10020430 ◽

2021 ◽

Vol 10 (2) ◽

pp. 430

Author(s):

Nico Hinz ◽

Anke Baranowsky ◽

Michael Horn ◽

Malte Kriegs ◽

Freya Sibbertsen ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Cancer Cells ◽

Crucial Role ◽

Breast Cancer Cells ◽

Molecular Mechanisms ◽

Combined Treatment ◽

Breast Cancer Patients ◽

Breast Cancer Bone Metastasis

Bone metastases frequently occur in breast cancer patients and lack appropriate treatment options. Hence, understanding the molecular mechanisms involved in the multistep process of breast cancer bone metastasis and tumor-induced osteolysis is of paramount interest. The serine/threonine kinase AKT plays a crucial role in breast cancer bone metastasis but the effect of individual AKT isoforms remains unclear. Therefore, AKT isoform-specific knockdowns were generated on the bone-seeking MDA-MB-231 BO subline and the effect on proliferation, migration, invasion, and chemotaxis was analyzed by live-cell imaging. Kinome profiling and Western blot analysis of the TGFβ/CTGF axis were conducted and metastasis was evaluated by intracardiac inoculation of tumor cells into NOD scid gamma (NSG) mice. MDA-MB-231 BO cells exhibited an elevated AKT3 kinase activity in vitro and responded to combined treatment with AKT- and mTOR-inhibitors. Knockdown of AKT3 significantly increased migration, invasion, and chemotaxis in vitro and metastasis to bone but did not significantly enhance osteolysis. Furthermore, knockdown of AKT3 increased the activity and phosphorylation of pro-metastatic HER2 and DDR1/2 but lowered protein levels of CTGF after TGFβ-stimulation, an axis involved in tumor-induced osteolysis. We demonstrated that AKT3 plays a crucial role in bone-seeking breast cancer cells by promoting metastatic potential without facilitating tumor-induced osteolysis.

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The circRNA DENND4C/miR-145-5p/HOXA9 Pathway Regulates Tumor Growth and Bone Metastasis in Breast Cancer

10.21203/rs.3.rs-95054/v1 ◽

2020 ◽

Author(s):

Menghai Zhu ◽

Chong Lian ◽

Gang Chen ◽

Peng Zou

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Tumor Growth ◽

Cancer Patients ◽

Statistical Significance ◽

Expression Patterns ◽

Luciferase Reporter ◽

Breast Cancer Patients ◽

Gene Assay ◽

Breast Cancer Bone Metastasis

Abstract BackgroundCircular RNAs (circRNAs) are involved in the occurrence and development of breast cancer bone metastasis. This study aims to identify whether the circRNA DENND4C/ miR145-5p/HOXA9 axis is involved in the regulation of cell invasion and migration and breast cancer progression.MethodscircRNA DENND4C, miR-145-5p and HOXA9 expression was measured in serum samples from healthy volunteers, breast cancer patients without bone metastasis and breast cancer patients with bone metastasis. Moreover, we analyzed the levels of circRNA DENND4C, miR‑145-5p and HOXA9 according to different conditions of differentiation, tumor volume and lymph node metastasis. The online software starBases and the dual-luciferase reporter gene assay were used to predict the relationship miR-145-5p, circRNA DENND4C and HOXA9 mRNA. MTT assays were performed to assess the effect of circRNA DENND4C on proliferation. To assess the proliferation of breast cancer cells among different groups. Statistical significance was determined byStudent's t‑test which was used for comparisons between two groups and one‑way analysis of variance followed by Tukey's post hoc test for comparisons between more than two groups.ResultsThe expression patterns of circRNA DENND4C, miR145-5p and HOXA9 were altered in patients with breast cancer bone metastasis. Notably, the stimulatory effects of circRNA DENND4C overexpression on HOXA9 were eliminated by miR-145-5p upregulation. circRNA DENND4C overexpression promotes proliferation, migration and invasiveness by regulating the miR-145-5p/HOXA9 axis. circRNA DENND4C downregulation suppresses proliferation, cell viability and invasiveness by regulating the miR-145-5p/HOXA9 axis. ConclusionOur study suggest that circRNA DENND4C/miR-145-5p/HOXA9 pathway was involved in tumor growth and bone metastasis in breast cancer. This findings may facilitate the development of potential therapeutic agents to improve the prognosis of patients with breast cancer bone metastasis.

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Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

Asian Pacific Journal of Tropical Medicine ◽

10.1016/s1995-7645(13)60128-5 ◽

2013 ◽

Vol 6 (9) ◽

pp. 732-738 ◽

Cited By ~ 3

Author(s):

Heng-Wei Zhang ◽

Xian-Fu Sun ◽

Ya-Ning He ◽

Jun-Tao Li ◽

Xu-Hui Guo ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Bioinformatics Analysis ◽

Related Gene ◽

Breast Cancer Bone Metastasis

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The role of IL-1B in breast cancer bone metastasis

Endocrine Related Cancer ◽

10.1530/erc-17-0309 ◽

2018 ◽

Vol 25 (7) ◽

pp. R421-R434 ◽

Cited By ~ 25

Author(s):

Claudia Tulotta ◽

Penelope Ottewell

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Tumour Microenvironment ◽

Tumour Cells ◽

Breast Cancer Patients ◽

Potential Biomarker ◽

Increased Risk ◽

Breast Cancer Bone Metastasis ◽

New Treatments

Approximately 75% of patients with late-stage breast cancer will develop bone metastasis. This condition is currently considered incurable and patients’ life expectancy is limited to 2–3 years following diagnosis of bone involvement. Interleukin (IL)-1B is a pro-inflammatory cytokine whose expression in primary tumours has been identified as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In this review, we discuss how IL-1B from both the tumour cells and the tumour microenvironment influence growth of primary breast tumours, dissemination into the bone metastatic niche and proliferation into overt metastases. Recent evidence indicates that targeting IL-1B signalling may provide promising new treatments that can hold tumour cells in a dormant state within bone thus preventing formation of overt bone metastases.

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