miR-9 Enhances the Chemosensitivity of AML Cells to Daunorubicin by Targeting the EIF5A2/MCL-1 Axis

Liu, Yan‐Hui; Lei, Pingchong; Qiao, Hong; Sun, Kai; Lu, Xiling; Bao, Fengchang; Yu, Ran; Lian, Cheng; Li, Yao; Chen, Wei

doi:10.7150/ijbs.29775

Cited by 28 publications

(12 citation statements)

References 35 publications

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“…[16][17][18] Our previous study indicated that miR-9 was closely related to the sensitivity of chemotherapy drugs. 19 We also identified a negative correlation between TUG1 and miR-9-5p, and the luciferase assay confirmed this result. However, the interactions between TUG1 and miRNAs that regulate Dox resistance in BC remains elusive.…”

Section: Introductionsupporting

confidence: 72%

Interactions Between lncRNA TUG1 and miR-9-5p Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2

Wang

Cheng²,

Zheng³

et al. 2020

OTT

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Purpose Breast cancer (BC) is one of the leading causes of cancer-related deaths. Chemoresistance of BC remains a major unmet clinical obstacle. TUG1 (taurine-upregulated gene 1), a long noncoding RNA (lncRNA), and microRNAs (miRNA) are implicated in therapeutic resistance. However, the interactions between TUG1 and miRNAs that regulate doxorubicin (Dox) resistance in BC remain elusive. Materials and Methods Expression of TUG1 and miR-9 was measured by real-time PCR. EIF5A2 (eukaryotic translation initiation factor 5A-2) was detected by Western blot. Transfection of siRNAs or miRNA inhibitors was applied to silence lncRNA TUG1, eIF5A2 or miR-9. Cell viability, proliferation, and apoptosis were determined by CCK-8 (cell counting kit-8), flow cytometry, and EdU (5-ethynyl-2ʹ-deoxyuridine) assays, respectively. The regulatory relationship between TUG1 and miR-9 was determined by a luciferase assay. Results LncRNA TUG1 was highly expressed in BC tissues and positively associated with Dox resistance in BC cell lines. SiRNA knockdown of TUG1 reversed Dox resistance in MCF-7/ADR cells. Mechanistically, TUG1 acted as a “sponge” for miR-9 and downregulated miR-9. Treatment with a miR-9 inhibitor blocked the effect of TUG1 siRNA, and knockdown of TUG1 inhibited the effects of miR-9. Furthermore, TUG1 inhibition of apoptosis induced by Dox involved miR-9 targeting of eIF5A2. Conclusion TUG1 modulates the susceptibility of BC cells to Dox by regulating the expression of eIF5A2 via interacting with miR-9. These results indicate that the lncRNA TUG1 may be a novel therapeutic target in breast cancer.

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Section: Introductionsupporting

confidence: 72%

Interactions Between lncRNA TUG1 and miR-9-5p Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2

Wang

Cheng²,

Zheng³

et al. 2020

OTT

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“…It has been reported that miR-9 could enhance sensitivity to cisplatin of NSLSC through inhibiting EIF5A2 expression [26]. Furthermore, miR-9 could enhance the chemosensitivity to daunorbicin in AML cells via regulating EIF5A2 [27]. As an oncogene or a tumor suppressor, MiR-9 also plays an important role in migration and invasion in HCC cells.…”

Section: Discussionmentioning

confidence: 99%

“…As previously reported, EIF5A2 may be a previous target of miR-9 [26,27].We used the TargetScan Human database to determine the mechanism of miR-9-induced chemosensitivity and its possible target genes. EIF5A2, which has been implicated as an oncogene that enhances chemoresistance in several cancers, harbored a potential miR-9 binding site ( Figure 4A).…”

Section: Mir-9 Targeted Eif5a2 In Hcc Cellsmentioning

confidence: 99%

Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition

Bao¹,

Zhang²,

Lu³

et al. 2020

Int. J. Biol. Sci.

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We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.

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“…Our previous work demonstrated that miR-9 rescues daunorubicin resistance by mediating eIF5A2 [16]. EIF5A2 is highly conserved throughout eukaryotic evolution and plays a role in mRNA translation, cellular proliferation, cellular differentiation, and inflammation [24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…We also identified a negative correlation between TUG1 and miR-9. We had previously shown that miR-9 regulates daunorubicin resistance through regulation of eukaryotic translation initiation factor 5A-2 (EIF5A2) [16]. However, whether TUG1 can regulate the chemoresistance of breast cancer via similar mechanisms remains unknown.…”

mentioning

confidence: 99%

Interactions between lncRNA TUG1 and miR-9 Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2

Wang

Cheng²,

Zheng³

et al. 2019

SSRN Journal

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Background: Breast cancer (BC) is one of the leading causes of cancer-related deaths. Chemoresistance of BC remains a major unmet clinical obstacle. TUG1 (Taurine upregulated gene 1), a long noncoding RNA (lncRNA), and microRNAs (miRNA) are implicated in therapeutic resistance. However, the interactions between TUG1 and miRNAs that regulate doxorubicin (Dox) resistance in BC remain elusive. Methods: Expression of TUG1 and miR-9 was measured by qRT-PCR (Quantitative real-time polymerase chain reaction). EIF5A2 (Eukaryotic translation initiation factor 5A-2) was detected by western blot. Transfection of siRNAs or miRNA inhibitors was applied to silence lncRNA TUG1, eIF5A2 or miR-9. Cell viability, proliferation, and apoptosis were determined by CCK-8 (Cell counting kit-8), flow cytometry, and EdU (5-ethynyl-2'-deoxyuridine) assays, respectively. The regulatory relationship between TUG1 and miR-9 was determined by a luciferase assay. Results: LncRNA TUG1 was highly expressed in BC tissues and positively associated with doxorubicin resistance in BC cell lines. SiRNA knockdown of TUG1 reversed doxorubicin resistance in MCF-7/ADR cells. Mechanistically, TUG1 acted as a 'sponge' for miR-9 and downregulated miR-9. Treatment with a miR-9 inhibitor blocked the effect of TUG1 siRNA, and knockdown of TUG1 inhibited the effects of miR-9. Furthermore, TUG1 inhibition of apoptosis induced by doxorubicin involved miR-9 targeting of eIF5A2. Conclusions: TUG1 modulates the susceptibility of BC cells to doxorubicin by regulating the expression of eIF5A2 via a miR-9-dependent mechanism. Background Breast cancer (BC) is one of the leading causes of cancer-related deaths, has the highest incidence of malignant tumors among women, and is a significant public health concern[1]. Doxorubicin (Dox) is an anthracycline drug that is commonly used in the effective treatment of breast cancer, and resistance to Dox is a major challenge in breast cancer treatment[2, 3]. Therefore, novel treatment approaches that enable clinicians and researchers to explore the potential mechanisms underlying BC chemoresistance and develop effective new strategies to enhance the efficacy of chemotherapy are Affiliations

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miR-9 Enhances the Chemosensitivity of AML Cells to Daunorubicin by Targeting the EIF5A2/MCL-1 Axis

Cited by 28 publications

References 35 publications

Interactions Between lncRNA TUG1 and miR-9-5p Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2

Interactions Between lncRNA TUG1 and miR-9-5p Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2

Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition

Interactions between lncRNA TUG1 and miR-9 Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2

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