iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling

Xiong, Ying; Sun, Fei; Dong, Peixin; Watari, Hidemichi; Yue, Junming; Yu, Meng‐Fei; Lan, Xi; Wang, Yin; Ma, Ze Biao

doi:10.1186/s13046-017-0520-6

Cited by 69 publications

(55 citation statements)

References 45 publications

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“…Notably, Yao et al, showed post-surgical patients with high expression of FBXL5 had shorter overall survival than patients with low FBXL5 expression [24]. Based on our data suggesting AM404's effect in CSC-like activity (Figure 2), and recent studies indicating FBXL5 regulating CRC metastasis [23,25,26], we then wanted to elucidate whether AM404 exerted its noted effects via FBXL5 in CRC cells [24,26,27]. We have therefore generated CRISPR-Cas9 mediated FBXL5-knockout in DLD-1 cell line ( Figure 6B and Figure S6).…”

Section: Fbxl5 Attenuates Am404-induced Anticancer Activitysupporting

confidence: 74%

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Repurposing Antibacterial AM404 As a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells

Ahmed

Jinks

Babaei‐Jadidi

et al. 2019

Cancers

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Tumour-promoting inflammation is involved in colorectal cancer (CRC) development and therapeutic resistance. However, the antibiotics and antibacterial drugs and signalling that regulate the potency of anticancer treatment upon forced differentiation of cancer stem-like cell (CSC) are not fully defined yet. We screened an NIH-clinical collection of the small-molecule compound library of antibacterial/anti-inflammatory agents that identified potential candidate drugs targeting CRC-SC for differentiation. Selected compounds were validated in both in vitro organoids and ex vivo colon explant models for their differentiation induction, impediment on neoplastic cell growth, and to elucidate the mechanism of their anticancer activity. We initially focused on AM404, an anandamide uptake inhibitor. AM404 is a metabolite of acetaminophen with antibacterial activity, which showed high potential in preventing CRC-SC features, such as stemness/de-differentiation, migration and drug-resistance. Furthermore, AM404 suppressed the expression of FBXL5 E3-ligase, where AM404 sensitivity was mimicked by FBXL5-knockout. This study uncovers a new molecular mechanism for AM404-altering FBXL5 oncogene which mediates chemo-resistance and CRC invasion, thereby proposes to repurpose antibacterial AM404 as an anticancer agent.

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Section: Fbxl5 Attenuates Am404-induced Anticancer Activitysupporting

confidence: 74%

“…Currently, there is no established data available for AM404 in colorectal cancer. Our data suggest that ubiquitin-ligase FBXL5 [24][25][26][27], might be a key target through which AM404 utilizes its pharmacological effects on CRC cells.…”

Section: Introductionmentioning

confidence: 85%

Repurposing Antibacterial AM404 As a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells

Ahmed

Jinks

Babaei‐Jadidi

et al. 2019

Cancers

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“…Here, we reported that miR-20a is downregulated in osteosarcoma and indicated that miR-20a is a tumorsupressor in osteosarcoma cell growth. miR-20a downregulation was reported in cutaneous squamous cell carcinoma, future science group www.futuremedicine.com hepatocellular carcinoma and pancreatic cancer cells [18][19][20], whereas its upregulation was shown in uveal melanoma, colorectal cancer and cervical cancer [21][22][23]. These controversial data indicate that the function of miR-20a is possibly tumor specific and highly dependent on its downstream target in various cancers.…”

Section: Discussionmentioning

confidence: 99%

MiRNA-20A Upregulates TAK1 and Increases Proliferation in Osteosarcoma Cells

Yuan

Zhao

et al. 2018

Future Oncol.

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Aim:The aim of this study is to explore the function of miR-20a in osteosarcoma. Materials & methods: miR-20a expression was measured by real-time PCR. miR-20a mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on colony formation and tumor growth. Moreover, relationships of miR-20a with TAK1 were investigated by western blot and luciferase activity. Results: We found that miR-20a was downregulated in osteosarcoma, and overexpression of miR-20a reduced colony formation and tumor growth. Furthermore, the data revealed that the function of miR-20a was probably exerted via targeting the TAK1 expression. Overexpression of miR-20a sensitizes the osteosarcoma cells to chemotherapeutic drugs. Conclusion: Our data identify the role of miR-20a in osteosarcoma growth, indicating its potential application in chemotherapy. Osteosarcoma is the most common primary malignant bone tumor with high morbidity in young adults and children, comprising 2.4% of all malignancies in pediatric patients and about 20% of all primary bone tumors [1]. It occurs mainly around regions with active bone growth and reparation. Osteosarcoma is highly aggressive and responded poorly to chemotherapy, and the 5-year survival rate for patients with metastatic osteosarcoma is only 14% [2]. Therefore, it is of extreme significance to elucidate novel molecular targets to develop alternative therapeutic target for this disease.miRNAs are a small family of noncoding RNAs that play important roles in the development of human diseases by negatively regulating gene expression at either post-transcriptional or translational levels [3,4]. Over the last decade, many miRNAs have been showed in regulating diverse biological events such as cell proliferation, differentiation and apoptotic processes [5][6][7], which are important in the development of cancer. Accumulated evidence indicated that aberrant expression of miRNAs associates with various types of cancer. These dysregulated miRNAs function as either oncogenes or tumor suppressors in carcinogenesis and progression of cancers [8,9]. Thus, to explore the aberrant miRNAs expression in osteosarcoma might lead to the discovery of novel miRNAs biomarkers.In this study, we found that miR-20a was downregulated in osteosarcoma samples and osteosarcoma cell lines, and the ectopic expression of miR-20a reduced cell colony formation in vitro and tumor growth in vivo. Furthermore, bioinformatic prediction and experimental validation revealed that the function of miR-20a was probably exerted via targeting the TAK1 expression. To translate these findings, overexpression of miR-20a sensitizes the osteosarcoma cells to chemotherapeutic drugs. Collectively, our data identify the key role of miR-20a in osteosarcoma growth, indicating its potential application in cancer chemotherapy.

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“…miR-20a can also inhibit proliferation and induce the apoptosis of hepatocellular carcinoma cells in vitro by targeting the anti-apoptotic member myeloid cell leukemia sequence 1 protein of the Bcl-2 family (48). The expression of miR-20a in glioma, cervical cancer, gastric cancer, lung carcinoma, neuroblastoma and prostate cancer, and its corresponding target genes and their functions, are presented in Table II (46,(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68). However, the upregulation or downregulation of miR-20a expression in a number of tumors is not consistent in numerous previous studies due to the differences in cell lines and limited sample sizes (47,(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79).…”

Section: Microrna-20a Overviewmentioning

confidence: 99%

“…However, the chemotherapy resistance of CRC cells is challenge in the treatment of patients with CRC (119). Studies have indicated that miR-20a induces cisplatin resistance in numerous cancers, potentially including in CRC (55,57,111,112). The miR-20a inhibitor can sensitize cisplatin-induced CRC cytotoxicity via the reactive oxygen species (ROS) pathway.…”

Section: Mir-20a May Be Used As a Monitoring Indicator During Chemothmentioning

confidence: 99%

Function and mechanisms of microRNA‑20a in colorectal cancer (Review)

et al. 2020

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Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-associated mortality worldwide. CRC currently has no specific biomarkers to promote its diagnosis and treatment and the underlying mechanisms regulating its pathogenesis have not yet been determined. MicroRNAs (miRs) are small, non-coding RNAs that exhibit regulatory functions and have been demonstrated to serve a crucial role in the post-transcriptional regulatory processes of gene expression that is associated with cell physiology and disease progression. Recently, abnormal miR-20a expression has been identified in a number of cancers types and this has become a novel focus within cancer research. High levels of miR-20a expression have been identified in CRC tissues, serum and plasma. In a recent study, miR-20a was indicated to be present in feces and to exhibit a high sensitivity to CRC. Therefore, miR-20a may be used as a marker for CRC and an indicator that can prevent the invasive examination of patients with this disease. Changes in the expression of miR-20a during chemotherapy can be used as a biomarker for monitoring resistance to treatment. In conclusion, miR-20a exhibits the potential for clinical application as a novel diagnostic biomarker and therapeutic target for use in patients with CRC. The present study focused on the role and mechanisms of miR-20a in CRC. Contents 1. Introduction 2. microRNA-20a overview 3. The mechanism of miR-20a in CRC 4. miR-20a can be used as a diagnostic marker in CRC 5. miR-20a may be used as a monitoring indicator during chemotherapy 6. Conclusion and prospects

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iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling

Cited by 69 publications

References 45 publications

Repurposing Antibacterial AM404 As a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells

Repurposing Antibacterial AM404 As a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells

MiRNA-20A Upregulates TAK1 and Increases Proliferation in Osteosarcoma Cells

Function and mechanisms of microRNA‑20a in colorectal cancer (Review)

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