“…21 In addition, evidences have been shown that miR-153 functioned as a tumor suppressor in several cancers including lung cancer, acute lymphoblastic leukemia and breast cancer. [22][23][24] In this study, we found that overexpression of miR-153-5p significantly induced the apoptosis of MDA-MB-231/PTX cells. In addition, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were enhanced by miR-153-5p overexpression.…”
Background: Paclitaxel (PTX) resistance is a main obstacle for the treatment of triplenegative breast cancers (TNBC). Evidences have shown that miR-153-5p could induce the apoptosis of breast cancer cells. Thus, this study aimed to investigate the effect of miR-153-5p on PTX-resistance TNBC cells. Methods: Cell Counting Kit-8, flow cytometry and wound healing assays were used to detect the viability, apoptosis and migration of MDA-MB-231/PTX cells, respectively. The luciferase reporter assay was used to explore the potential binding targets of miR-153-5p. The expressions of CDK1, cyclin B1 and p-Akt in MDA-MB-231/PTX cells were detected with Western blot. In vivo animal study was performed finally. Results: In this study, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were significantly enhanced following transfection with miR-153-5p. In addition, overexpression of miR-153-5p markedly enhanced the pro-apoptotic effect of PTX on MDA-MB-231/PTX cells. Luciferase reporter assay validated that cyclin-dependent kinase 1 (CDK1) was a potential binding target of miR-153-5p. Moreover, overexpression of miR-153-5p prominently increased PTX-induced cell cycle arrest at G2/M phase in MDA-MB-231/PTX cells via downregulation of CDK1, cyclin B1 and p-Akt. In vivo experiments confirmed that overexpression of miR-153-5p notably enhanced PTX sensitivity in MDA-MB-231/PTX xenograft model. Conclusion: We found that overexpression of miR-153-5p could reverse PTX resistance in PTX-resistant TNBC cells via inducing G2/M phase arrest, indicating that miR-153-5p may be a promising agent for patients with PTX-resistant TNBC.
“…21 In addition, evidences have been shown that miR-153 functioned as a tumor suppressor in several cancers including lung cancer, acute lymphoblastic leukemia and breast cancer. [22][23][24] In this study, we found that overexpression of miR-153-5p significantly induced the apoptosis of MDA-MB-231/PTX cells. In addition, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were enhanced by miR-153-5p overexpression.…”
Background: Paclitaxel (PTX) resistance is a main obstacle for the treatment of triplenegative breast cancers (TNBC). Evidences have shown that miR-153-5p could induce the apoptosis of breast cancer cells. Thus, this study aimed to investigate the effect of miR-153-5p on PTX-resistance TNBC cells. Methods: Cell Counting Kit-8, flow cytometry and wound healing assays were used to detect the viability, apoptosis and migration of MDA-MB-231/PTX cells, respectively. The luciferase reporter assay was used to explore the potential binding targets of miR-153-5p. The expressions of CDK1, cyclin B1 and p-Akt in MDA-MB-231/PTX cells were detected with Western blot. In vivo animal study was performed finally. Results: In this study, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were significantly enhanced following transfection with miR-153-5p. In addition, overexpression of miR-153-5p markedly enhanced the pro-apoptotic effect of PTX on MDA-MB-231/PTX cells. Luciferase reporter assay validated that cyclin-dependent kinase 1 (CDK1) was a potential binding target of miR-153-5p. Moreover, overexpression of miR-153-5p prominently increased PTX-induced cell cycle arrest at G2/M phase in MDA-MB-231/PTX cells via downregulation of CDK1, cyclin B1 and p-Akt. In vivo experiments confirmed that overexpression of miR-153-5p notably enhanced PTX sensitivity in MDA-MB-231/PTX xenograft model. Conclusion: We found that overexpression of miR-153-5p could reverse PTX resistance in PTX-resistant TNBC cells via inducing G2/M phase arrest, indicating that miR-153-5p may be a promising agent for patients with PTX-resistant TNBC.
“…In addition to regulating tumor cell infiltration and metastasis, miR‐153‐3p has also been shown to regulate chemosensitivity of cancer cells. MiR‐153‐3p has been reported to overcome the resistance of lung cancer cells to gefitinib by downregulating ABCE1 . Our recent studies have shown that MiR‐153‐3p inhibits the migration and invasion of ESCC cells whereas miR‐153 antagomir promotes migration and invasion of normal esophageal epithelial cells .…”
Section: Discussionmentioning
confidence: 93%
“…MiR-153-3p has been reported to overcome the resistance of lung cancer cells to gefitinib by downregulating ABCE1. 26 Our recent studies have shown that MiR-153-3p inhibits the migration and invasion of ESCC cells whereas miR-153 antagomir promotes migration and invasion of normal esophageal epithelial cells. 3 Therefore, whether miR-153-3p regulates the proliferation of ESCC cells and confers sensitivity to cisplatin chemotherapy is not clear.…”
Background
Our recent studies have indicated that miR‐153‐3p is downregulated in the esophageal squamous cell carcinoma (ESCC) cell lines and tissues. Upregulation of miR‐153‐3p was found to inhibit migration and invasion of ESCC cells. However, whether miR‐153‐3p regulates the cisplatin sensitivity in ESCC cells remains unclear. In this study, we explored whether and how miR‐153‐3p regulates the proliferation and confers cisplatin resistance in ESCC by targeting the Nrf‐2 protein.
Methods
Eca109 cell line was transfected with microRNA‐153‐3p mimics or Nrf‐2siRNA and cell proliferation and cisplatin resistance were studied. A dual‐luciferase reporter assay was performed on Eca109 cells cotransfected with the wild‐type/mutant 3′UTR sequences of Nrf‐2 and control or microRNA‐153‐3p mimics. We determined the correlation between microRNA‐153‐3p and Nrf‐2 expression in human ESCC samples and explored the effect of Nrf‐2 in the overall survival rate of ESCC patients.
Results
MiR‐153‐3p significantly suppressed cell proliferation and increased the sensitivity of Eca‐109 cells to cisplatin. MiR‐153‐3p showed a negative correlation with Nrf‐2 in human esophageal carcinoma tissues. MiR‐153‐3p suppressed the expression of Nrf‐2 via binding to its 3′‐UTR region. Furthermore, inhibition of Nrf‐2 also decreased cell proliferation and increased the sensitivity of Eca109 cells to cisplatin. High expression of Nrf‐2 in human ESCC samples was associated with poor overall survival of ESCC patients.
Conclusion
MiR‐153‐3p inhibits cell proliferation and confers cisplatin resistance by downregulating Nrf‐2 expression in Eca‐109 cells. Thus, miR‐153‐3p/Nrf‐2 may play an important role in conferring cisplatin resistance in ESCC. Nrf‐2 appears to be a promising therapeutic target for ESCC.
“… 194 MiR-153 directly targeted ABCE1 to inhibit gefitinib resistance in lung cancer, which may provide a therapeutic target to reverse the resistance to gefitinib in the future. 195 Fig. 6 Epitranscriptomic and epiproteomic modifications could be the potential therapeutic targets in cancers.…”
Section: Epitranscriptomic and Epiproteomic Modifications As Therapeumentioning
Drug resistance is a major hurdle in cancer treatment and a key cause of poor prognosis. Epitranscriptomics and epiproteomics are crucial in cell proliferation, migration, invasion, and epithelial–mesenchymal transition. In recent years, epitranscriptomic and epiproteomic modification has been investigated on their roles in overcoming drug resistance. In this review article, we summarized the recent progress in overcoming cancer drug resistance in three novel aspects: (i) mRNA modification, which includes alternative splicing, A-to-I modification and mRNA methylation; (ii) noncoding RNAs modification, which involves miRNAs, lncRNAs, and circRNAs; and (iii) posttranslational modification on molecules encompasses drug inactivation/efflux, drug target modifications, DNA damage repair, cell death resistance, EMT, and metastasis. In addition, we discussed the therapeutic implications of targeting some classical chemotherapeutic drugs such as cisplatin, 5-fluorouridine, and gefitinib via these modifications. Taken together, this review highlights the importance of epitranscriptomic and epiproteomic modification in cancer drug resistance and provides new insights on potential therapeutic targets to reverse cancer drug resistance.
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