Modulatory role of miR-205 in angiogenesis and progression of thyroid cancer

Salajegheh, Ali; Vosgha, Haleh; Rahman, Atiqur; Amin, Moein; Smith, Robert A.; Lam, Alfred King‐Yin

doi:10.1530/jme-15-0182

Cited by 44 publications

(41 citation statements)

References 28 publications

(33 reference statements)

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“…Based on the role of miR-205 in inhibiting the proliferation of pancreatic cancer, we next performed cell cycle analysis. We observed a significant increase in the percentage of MIA PaCa-2R cells at G0/G1 phase as reported earlier after miR-205 overexpression [36,37], which further increases after GEM-treatment (Fig. 4A).…”

Section: Discussionsupporting

confidence: 88%

Chemosensitization and inhibition of pancreatic cancer stem cell proliferation by overexpression of microRNA-205

et al. 2017

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Treatment of pancreatic cancer with gemcitabine (GEM) is limited due to its rapid plasma metabolism and development of chemoresistance. MicroRNA (miRNA) regulates cancer stem cell (CSC) maintenance and induces chemoresistance in cancer cells. In this study, we observed differential downregulation of miR-205 (miR-205-5p) in human pancreatic cancer tissues and cells. Compared to GEM-sensitive MIA PaCa-2 cells, miR-205 was highly downregulated in GEM-resistant MIA PaCa-2R cells. Lentivirus-mediated overexpression of miR-205 inhibits MIA PaCa-2R cell proliferation after GEM-treatment. Further investigation confirmed that miR-205 alone significantly reduces the proliferation of CSCs and tumor growth in mouse models. However, miR-205 in combination with GEM was more efficient in reducing the proliferation of CSCs and 3D spheroids. Moreover, miR-205 overexpressing MIA PaCa-2R cells induced orthotopic tumor growth was significantly inhibited after intravenous administration of GEM-conjugated methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate)-graft-gemcitabine-graft-dodecanol (mPEG-b-PCC-g-GEM-g-DC) (mPEG-b-PCC-g-GEM-g-DC) polymeric micelles. Also, a reduction in CSCs, EMT and chemoresistance markers was observed in miR-205 overexpressing MIA PaCa-2R cells. Immunohistochemical analysis of orthotopic tumors showed a decrease in drug resistance protein caveolin-1 and cell proliferation marker Ki-67 in combination treatment. Overall, our findings suggest that miR-205 resensitizes GEM-resistant pancreatic cancer cells to GEM and acts as a tumor suppressor miRNA.

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Section: Discussionsupporting

confidence: 88%

Chemosensitization and inhibition of pancreatic cancer stem cell proliferation by overexpression of microRNA-205

et al. 2017

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“…Bioinformatic analysis indicates that both VEGFA and FGF2 are potential targets for miR-205 (Figure 3a), and this has been confirmed for VEGFA in osteosarcoma 24 , thyroid cancer 25 and breast cancer MDA-MB-231 cells. 34 VEGFA and FGF2 promote therapy resistance in a number of cancers 35, 36, 37, 38 and, reassuringly, we have confirmed their overexpression both at the mRNA and protein levels in both MCF-7/A02 and CALDOX cells (Figure 3b).…”

Section: Resultsmentioning

confidence: 75%

“…MiR-205 restoration decreased cell proliferation in the absence of drug by 24–37% (Figure 2c), and cell cycle analysis showed a significant arrest and accumulation of cells in the G0/G1 phase (Supplementary Figure S1B), which is consistent with data in human osteosarcoma 24 and thyoid carcinoma. 25 Moreover, miR-205 impaired proliferation to a much higher extent in the presence of doxorubicin or taxol (reduction between 75 and 91% Figure 2c). Thus overexpression of miR-205 restores sensitivity to doxorubicin and taxol in drug-resistant breast cancer cells.…”

Section: Resultsmentioning

confidence: 94%

miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

et al. 2016

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MicroRNAs (miRNAs) have critical roles in regulating cancer cell survival, proliferation and sensitivity to chemotherapy. The potential application of using miRNAs to predict chemotherapeutic response to cancer treatment is highly promising. However, the underlying mechanisms of chemotherapy response control by miRNAs remain to be fully identified and their prognostic value has not been fully evaluated. Here we show a strong correlation between miR-205 expression and chemosensitivtiy to TAC (docetaxol, doxorubicin plus cyclophosphamide), a widely-used neoadjuvant chemotherapy (NAC) regimen, for breast cancer patients. High level of miR-205 predicted better response to TAC regimen NAC in breast cancer patients. We found miR-205 downregulated in both MCF-7/A02 and CALDOX cells, two drug-resistant derivatives of MCF-7 and Cal51 cells, and its ectopic expression led to an increase in apoptosis resensitization of both drug-resistant cell lines to doxorubicin and taxol. We further show that miR-205 directly binds VEGFA and FGF2 mRNA 3′-UTRs and confirm that miR-205 levels are negatively correlated with VEGFA and FGF2 mRNA expression in breast cancer patients. Adding VEGFA and FGF2 exogenously to chemosensitive breast cancer cells and chemoresistant cells with miR-205 overexpression led to drug resistance. Consistently, low VEGFA and FGF2 expression correlated with better response to NAC in breast cancer patients. In addition, inhibition of tumor growth and resensitization to doxorubicin were also observed in mouse tumor xenografts from cells overexpressing miR-205. Taken together, our data suggest that miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis. MiR-205 may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment.

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“…An emerging miRNA with possible prognostic application in DTC is miR-205. Indeed, Salajegheh and coworkers recently demonstrated an underexpression of miR-205 in DTC specimens, compared with that in normal tissues, and, more importantly, associated the entity of the dysregulation to distant metastases and advanced stages (Salajegheh et al 2015). In the same paper, authors also provided pre-clinical support to their finding demonstrating both anti-angiogenic and tumoursuppressive action of miR-205 in thyroid cancer cell lines.…”

Section: :11mentioning

confidence: 86%

Application of molecular biology of differentiated thyroid cancer for clinical prognostication

Marotta¹,

Sciammarella²,

Colao³

et al. 2016

Endocrine-Related Cancer

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Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF V600E is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF V600E and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated. 23:11Review V Marotta et al. Molecular prognosis in thyroid cancer

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Modulatory role of miR-205 in angiogenesis and progression of thyroid cancer

Cited by 44 publications

References 28 publications

Chemosensitization and inhibition of pancreatic cancer stem cell proliferation by overexpression of microRNA-205

Chemosensitization and inhibition of pancreatic cancer stem cell proliferation by overexpression of microRNA-205

miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

Application of molecular biology of differentiated thyroid cancer for clinical prognostication

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