MiR-139-5p reverses CD44+/CD133+-associated multidrug resistance by downregulating <i>NOTCH1</i> in colorectal carcinoma cells

Xu, Ke; Shen, Ke; Liang, Xin; Li, Yueqi; Nagao, Norio; Li, Jiyu; Liu, Jianwen; Yin, Peihao

doi:10.18632/oncotarget.12611

Cited by 38 publications

(29 citation statements)

References 37 publications

(39 reference statements)

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“…These drug-resistant cells have more CD44-and CD133-positive populations than non-resistant cells. As expected, the over-expression of miR-139-5p renders CD44-and CD133-positive cells sensitive to several anti-cancer drugs [123]. Furthermore, Notch 3 is directly targeted by miR-136-5p; therefore, CSC spheroid formation is restricted by this miRNA [124] (Table 4).…”

Section: Mirnas Regulating Notch Receptor 1 Andsupporting

confidence: 57%

“…Notch signaling is also affected by miRNAs that post-transcriptionally regulate the levels of Notch receptors. Notch 1 is targeted by miR-34-5p and miR-139-5p in breast cancer and colorectal carcinoma cells, respectively [122,123]. In doxorubicin-resistant breast cancer cells, miR-34-5p is down-regulated compared to parental cells, implying the possibility that this miRNA is pertinent to therapeutic resistance.…”

Section: Mirnas Regulating Notch Receptor 1 Andmentioning

confidence: 99%

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MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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Section: Mirnas Regulating Notch Receptor 1 Andsupporting

confidence: 57%

Section: Mirnas Regulating Notch Receptor 1 Andmentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

View full text Add to dashboard Cite

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“…Furthermore, it has been pointed out that disruptions of several oncogenic signaling pathways are participating in the oncogenesis of CRC, such as Notch signaling (5,6). As recorded, Notch signaling has been generally known to play prominent roles in promoting self-renewal of intestinal and colon stem cells and maintaining normal intestinal homeostasis by regulating cell proliferation, differentiation and apoptosis in the determination of cell fate (7,8).…”

Section: Introductionmentioning

confidence: 99%

Effects of RUNX3 mediated Notch signaling pathway on biological characteristics of colorectal cancer cells

Meng

2017

International Journal of Oncology

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This study investigated the effects of runt-related transcription factor 3 (RUNX3) mediated Notch pathway on the biological behavior of colorectal cancer (CRC) SW260 cells. CRC tissues and para-carcinoma tissues were collected from 182 CRC patients who had undergone surgical treatment between January 2008 and December 2010. Immunohistochemical staining with streptavidin-peroxidase (SP) was used to detect RUNX3, Notch1 and Jagged 1 expression levels. CRC SW260 cells were divided into the following groups: Control group, si-NC group, si-RUNX3 group, DAPT group, si-RUNX3+DAPT group, and si-NC+DAPT group. Expression levels of RUNX3, and Notch signaling related genes were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting in vitro. Besides, MTT, soft agar colony formation, Annexin V-FITC/PI double staining and Transwell were performed to analyze the effects of RUNX3 on cell growth and metastasis. Lower positive expression rate of RUNX3 and higher positive expression rate of Notch1 and Jagged 1 were observed in CRC tissues than those in normal adjacent tissues with a negative correlation, and the expression levels were associated with the differentiation degree, TNM staging, lymph node metastasis and tumor invasion depth (all P<0.05). RUNX3 expression was reduced in si-RUNX3 and si-RUNX3+DAPT group but the expression levels of Notch signaling related genes were markedly increased in si-RUNX3 group or decreased in DAPT and si-NC+DAPT group, as compared with those in the control group (all P<0.05). In addition, the proliferation, colony formation, migration and invasion abilities of SW260 cells were enhanced in si-RUNX3 group but were restricted in DAPT and si-NC+DAPT group, which was contrary to cell apoptosis (all P<0.05). RUNX3 contributes to attenuate the proliferation and metastasis of CRC cells, and promotes cell apoptosis through inhibition of Notch signaling pathway.

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“…Among these cancer-related miRNAs, miR-139-5p is usually downregulated in cancers and has been shown to suppress cell proliferation, migration and invasion in several cancers such as glioblastoma, colorectal cancer, non-small cell lung cancer, and ovarian cancer [32][33][34][35]. More importantly, the downregulation of miR-139-5p is reportedly associated with multidrug resistance in colorectal and breast cancers [36][37][38]. However, the role of miR-139-5p in the chemoresistance of ovarian cancer is unclear.…”

Section: Discussionmentioning

confidence: 99%

Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun

Jiang

Jia

et al. 2018

Cell Physiol Biochem

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Background/Aims: In platinum-based chemotherapy for ovarian cancer, acquired drug resistance is a frequent occurrence. Because recent studies have demonstrated that dysregulation of microRNAs (miRNAs) is partly responsible for the induction of acquired drug resistance in cancers, we hypothesized that correcting the dysregulation of key miRNAs would reverse the acquired resistance to platinum-based drugs in ovarian cancer. Methods: Cisplatin-resistant SKOV3 and A2780 ovarian cancer cell lines (SKOV3-R and A2780-R, respectively) were established by long-term exposure to cisplatin. MTT assays were performed to evaluate the viability of SKOV3, SKOV3-R, A2780, and A2780-R cells. Quantitative PCR was used to examine the expression of miR-139-5p in these cell lines. The regulatory mechanism was confirmed by western blot analysis and luciferase reporter assays. After treatment with miR-139-5p and cisplatin, mitochondrial membrane potential and apoptosis were measured by using flow cytometry. Interaction with c-Jun and activating transcription factor 2 (ATF2) was evaluated by co-immunoprecipitation. Expression of B-cell lymphoma-extra large (Bcl-xl) and activation of caspase-9 and caspase-3 were detected by western blotting. Results: Expression of miR-139-5p was decreased in SKOV3-R and A2780-R cells. Recovery of miR-139-5p increased the sensitivity of SKOV3-R and A2780-R cells to cisplatin treatment, inhibited the interaction of c-Jun and ATF2, and decreased Bcl-xl expression in SKOV3-R and A2780-R cells. Expression of miR-139-5p promoted cisplatin-induced mitochondrial apoptosis through binding the 3′ untranslated region of c-Jun mRNA. Conclusion: Recovery of miR-139-5p suppressed the expression of c-Jun and thus reversed cisplatin-resistance in ovarian cancer.

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MiR-139-5p reverses CD44+/CD133+-associated multidrug resistance by downregulating NOTCH1 in colorectal carcinoma cells

Cited by 38 publications

References 37 publications

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Effects of RUNX3 mediated Notch signaling pathway on biological characteristics of colorectal cancer cells

Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun

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