Cotargeting of miR‐126‐3p and miR‐221‐3p inhibits PIK3R2 and PTEN, reducing lung cancer growth and metastasis by blocking AKT and CXCR4 signalling

Paolo, Daniela Di; Pontis, Francesca; Moro, Massimo; Centonze, Giovanni; Bertolini, Giulia; Milione, Massimo; Mensah, Mavis; Segale, Miriam; Petraroia, Ilaria; Borzi, Cristina; Suatoni, Paola; Brignole, Chiara; Perri, Patrizia; Ponzoni, Mirco; Pastorino, Ugo; Sozzi, Gabriella; Fortunato, Orazio

doi:10.1002/1878-0261.13036

Cited by 21 publications

(12 citation statements)

References 44 publications

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“…According to a study by di Paolo et al, miR-221-3p inhibition combined with miR-126-3p augmentation induced tumour apoptosis [ 60 ]. This method was also well tolerated by normal cells [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…The miR-221/222 cluster was found to be overexpressed in the NSCLC [ 40 , 60 ]. MiR-221’s increased expression has been linked to a worse prognosis in lung cancer patients [ 60 ] and could serve as a prognostic tool [ 7 ]. Plasma miR-222-3p’s expression was found to be particularly upregulated in the NSCLC patients in comparison to healthy subjects but not in comparison to subjects with other lung diseases [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

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The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

Szczyrek

Bitkowska

Jutrzenka

et al. 2022

JPM

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Lung cancer remains a leading cause of cancer-related deaths worldwide, overtaking colon, breast, and prostate cancer-related deaths. Due to the limited diagnostic possibilities, it is often diagnosed after it has reached an advanced stage. The delayed diagnosis significantly worsens the patient’s prognosis. In recent years, we have observed an increased interest in the use of microRNAs (miRNAs) as diagnostic, predictive, and prognostic markers in non-small-cell lung cancer (NSCLC). The abnormal expression levels of the miRNAs could be used to detect NSCLC in its early stages while it is still asymptomatic. This could drastically improve the clinical outcome. Furthermore, some miRNAs could serve as promising predictive and prognostic factors for NSCLC. Some of the currently available studies have shown a correlation between the miRNAs’ levels and the sensitivity of tumour cells to different treatment regimens. Analysing and modulating the miRNAs’ expression could be a way to predict and improve the treatment’s outcome.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

Szczyrek

Bitkowska

Jutrzenka

et al. 2022

JPM

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“… 50 Interestingly, miR-221-3p was highly expressed in lung cancer, and the inhibition of miR-221-3p expression reduced the growth and metastasis of lung cancer. 51 Exosomal miR-10b-5p not only promoted the progression of glioma and gastric cancer, 52 , 53 but also played an important role in the early diagnosis of liver cancer and NSCLC, 54 , 55 especially lung adenocarcinoma. 56 All these previous studies suggest that the above miRNAs may be involved in exosomal EGFR-mediated EMT induced by HPV-16 E7 oncoprotein in NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo

Zhou

Zhan

et al. 2022

Cancer Biology & Therapy

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Our previous studies have demonstrated that human papillomavirus (HPV)-16 E7 oncoprotein promoted epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells. Moreover, recent studies have found that exosomes can mediate EMT of NSCLC cells and epidermal growth factor receptor (EGFR) is related to the progression of NSCLC. Here, we further investigated the role of exosomal EGFR in HPV-16 E7-induced EMT of NSCLC cells. Our results showed that the exosomes derived from the stable HPV-16 E7-overexpressing A549 and NCI-H460 NSCLC cells (E7 Exo) significantly increased migration, invasion, and proliferation abilities of NSCLC cells as compared with the exosomes derived from empty vector-infected NSCLC cells (ev Exo). Moreover, both in vitro and in vivo results demonstrated that E7 Exo dramatically enhanced EMT of NSCLC cells and promoted the growth of subcutaneous NSCLC xenografts. Additionally, HPV-16 E7 enhanced the expression of EGFR and p-EGFR in both NSCLC cells and exosomes. Furthermore, the inhibition of EGFR activation or exosome secretion suppressed E7 Exo-induced migration, invasion, and EMT of NSCLC. Moreover, 12 kinds of differentially expressed miRNAs between E7 Exo and ev Exo (fold change≥2, P ≤ .05) were screened out, of which 7 miRNAs were up-regulated while 5 miRNAs were down-regulated in A549 E7 Exo. Taken together, our findings suggest that exosomal EGFR is involved in HPV-16 E7-induced EMT of NSCLC cells, which may play a key role in the progression of HPV-related NSCLC.

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“…More recently, it has been reported that high levels of miR-17 by targeting LKB1 identify NSCLC patients who are eligible for metabolic therapeutic strategy because they show sensitivity to energetic stress condition [ 12 ]. Moreover, the simultaneous modulation of miR-126-3p and miR-221-3p inhibits the phosphatase and tensin homolog (PTEN) and the phosphoinositide-3-kinase receptor 2 (PI3KR2), thus reducing metastatic dissemination of lung cancer cells [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-486-5p Targets CD133+ Lung Cancer Stem Cells through the p85/AKT Pathway

et al. 2022

Self Cite

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Despite improvements in therapies and screening strategies, lung cancer prognosis still remains dismal, especially for metastatic tumors. Cancer stem cells (CSCs) are endowed with properties such as chemoresistance, dissemination, and stem-like features, that make them one of the main causes of the poor survival rate of lung cancer patients. MicroRNAs (miRNAs), small molecules regulating gene expression, have a role in lung cancer development and progression. In particular, mir-486-5p is an onco-suppressor miRNA found to be down-modulated in the tumor tissue of lung cancer patients. In this study, we investigate the role of this miRNA in CD133+ lung CSCs and evaluate the therapeutic efficacy of coated cationic lipid-nanoparticles entrapping the miR-486-5p miRNA mimic (CCL-486) using lung cancer patient-derived xenograft (PDX) models. In vitro, miR-486-5p overexpression impaired the PI3K/Akt pathway and decreased lung cancer cell viability. Moreover, miR-486-5p overexpression induced apoptosis also in CD133+ CSCs, thus affecting the in vivo tumor-initiating properties of these cells. Finally, we demonstrated that in vivo CCL-486 treatment decreased CD133+ percentage and inhibited tumor growth in PDX models. In conclusion, we provided insights on the efficacy of a novel miRNA-based compound to hit CD133+ lung CSCs, setting the basis for new combined therapeutic strategies.

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Cotargeting of miR‐126‐3p and miR‐221‐3p inhibits PIK3R2 and PTEN, reducing lung cancer growth and metastasis by blocking AKT and CXCR4 signalling

Abstract: Co-targeting of miR-126-3p and miR-221-3p inhibits PIK3R2 and PTEN, reducing lung cancer growth and metastasis by blocking AKT and CXCR4 signaling

Cited by 21 publications

References 44 publications

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo

MiR-486-5p Targets CD133+ Lung Cancer Stem Cells through the p85/AKT Pathway

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