Serum miR-4530 sensitizes breast cancer to neoadjuvant chemotherapy by suppressing RUNX2

Wang, Xiaoxiao; Ye, Fu-Gui; Zhang, Jie; Li, Junjing; Chen, Qing-Xia; Lin, Peiyang; Song, Chuan-Gui

doi:10.2147/cmar.s172205

Cited by 17 publications

(16 citation statements)

References 26 publications

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“…Accumulating evidences have confirmed the oncogenic role of RUNX2 in several cancers, and it has also been associated with the prognosis of patients with recurrence and metastasis [42][43][44][45][46]. Therefore, we investigated the potential role of RUNX2 in human CRC.…”

Section: Discussionmentioning

confidence: 98%

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

et al. 2020

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Background Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial–mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation. Methods We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues. Results We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter. Conclusions Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells.

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Section: Discussionmentioning

confidence: 98%

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

et al. 2020

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“…Moreover, elevated levels of miR-21 are associated with poor DFS and OS, and high miR-200c is associated with reduced DFS [204]. Serum miR-4530 levels are associated with sensitivity to NCT: in sensitive patients, miR-4530 is higher than in resistant subjects (AUC = 0.66, 98% sensitivity, and 86% specificity) [205].…”

Section: Mirnas As Tumor Biomarkersmentioning

confidence: 99%

“…The miR-411-5p + miR-382-5p + miR-376c-3p + miR-375 + miR-205-5p + miR-194-5p + miR-21-5p panel accurately predicted BC patients who would develop recurrence after tumor removal and treatment [203], while the miR-940 + miR-451a + miR-17-3p + miR-16-5p panel predicted one- and two-year OS of HER + mBC patients treated with trastuzumab [192]. After chemotherapy treatment, the miR-125b + miR-21 panel efficiently identified responder BC patients [196], miR-4530 sensitive patients [205], and the miR-205 + miR-19a panel resistant luminal A BC patients [193]. Finally, miR-200b discriminated CTC-positive from CTC-negative cases [216], miR-125b identified TNBC patients [189], and the miR-425 + miR-365 + miR-145 + miR-143 + miR-139-5p + miR-133a + miR-107 + miR-18a + miR-15a panel ER + BC patients [189].…”

Section: Mirnas As Tumor Biomarkersmentioning

confidence: 99%

Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Common Solid Tumors: Focus on Lung, Breast, Prostate Cancers, and Osteosarcoma

Bottani

Banfi

Lombardi

2019

JCM

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An early cancer diagnosis is essential to treat and manage patients, but it is difficult to achieve this goal due to the still too low specificity and sensitivity of classical methods (imaging, actual biomarkers), together with the high invasiveness of tissue biopsies. The discovery of novel, reliable, and easily collectable cancer markers is a topic of interest, with human biofluids, especially blood, as important sources of minimal invasive biomarkers such as circulating microRNAs (miRNAs), the most promising. MiRNAs are small non-coding RNAs and known epigenetic modulators of gene expression, with specific roles in cancer development/progression, which are next to be implemented in the clinical routine as biomarkers for early diagnosis and the efficient monitoring of tumor progression and treatment response. Unfortunately, several issues regarding their validation process are still to be resolved. In this review, updated findings specifically focused on the clinical relevance of circulating miRNAs as prognostic and diagnostic biomarkers for the most prevalent cancer types (breast, lung, and prostate cancers in adults, and osteosarcoma in children) are described. In addition, deep analysis of pre-analytical, analytical, and post-analytical issues still affecting the circulation of miRNAs’ validation process and routine implementation is included.

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“…Contrasting evidence regarding miR-4443 were reported in several cancer settings, such as breast and ovarian cancer [ 23 , 24 , 25 ]. Only one study has associated the high expression of miR-4530 with chemosensitivity in breast cancer [ 26 ]. This miRNA directly targets Runt-related transcription factor 2 ( RUNX2) that interacts with p53 and is correlated with poor clinical outcomes and resistance to anthracylines [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Only one study has associated the high expression of miR-4530 with chemosensitivity in breast cancer [ 26 ]. This miRNA directly targets Runt-related transcription factor 2 ( RUNX2) that interacts with p53 and is correlated with poor clinical outcomes and resistance to anthracylines [ 26 ]. Therefore, it is interesting to assess whether miR-4454 and miR-4530 are targeting the same pathway or different pathways but likewise responsible for the poor prognosis and more aggressive phenotype of cancer.…”

Section: Discussionmentioning

confidence: 99%

Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

Pratama

Visintin

Crocè

et al. 2020

Cancers

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The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD). The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC.

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Serum miR-4530 sensitizes breast cancer to neoadjuvant chemotherapy by suppressing RUNX2

Cited by 17 publications

References 26 publications

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Common Solid Tumors: Focus on Lung, Breast, Prostate Cancers, and Osteosarcoma

Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

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