MiR-200b and miR-15b regulate chemotherapy-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting BMI1

Sun, Lijuan; Yao, Yihong; Liu, B.; Lin, Zeyu; Lin, Ling; Yang, Mei; Zhang, W.; Chen, W.; Pan, Chaobin; Liu, Qiang; Song, Erwei; Li, J.

doi:10.1038/onc.2011.263

Cited by 225 publications

(222 citation statements)

References 43 publications

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“…15 On the contrary, miR-200b and miR-15b reverse chemotherapy induced epithelial-mesenchymal transition (EMT) in human tongue cancer cells by targeting BMI1. 16 We have previously identified an A549/CDDP res cell line that is resistant to CDDP and found that a series of miRNAs CONTACT Jie Fan jif7@pitt.edu; Gening Jiang jgn1121@163.com and mRNAs in these CDDP resistant cells are expressed differently from those in the parental A549 cells. 17 In this study, we aimed to identify active transcriptional and posttranscriptional regulatory pathways in NSCLC based on CDDP resistancerelated expression profiles of mRNA and miRNA as well as regulation of miRNA and transcription factors (TF).…”

Section: Introductionmentioning

confidence: 99%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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Background: Lung cancer is the most common cancer that is caused by perturbation of regulatory pathways rather than dysfunction of a single gene. Cisplatin (CDDP; cis-diamminedichloroplatinum II) is the first member of a class of platinum-containing anti-cancer medication, which binds to DNA and triggers apoptosis. CDDP-based chemotherapy is used to treat various types of cancers. However, the efficacy of CDDP in the treatment of non-small-cell lung cancer (NSCLC) is limited by acquired drug resistance. MicroRNAs have recently emerged as key regulators of cancers, and miR-26a is one of downregulated miRNAs in A549/CDDP res cell line. This study aimed to investigate the role of miR-26a in CDDP resistance in NSCLC as well as the underlying mechanisms.Methods: In this study, we analyzed expressional profiles of CDDP resistance-related mRNA, miRNA, and transcription factors (TF) that regulate miRNA expression in NSCLC. A549 cells were treated with CDDP, miR-26a mimic, or miR-26a inhibitor, and followed by biological analysis including drug sensitivity assay, colony formation assay, terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay, and cell cycle analysis. Luciferase assay was used to determine the target of miR-26a. The regulation of miR-26a in Akt pathway was measured by western blot.Results: High mobility group A (HMGA) 2 was identified as the target of miR-26a. Overexpression of miR26a in A549 cells inhibited G1-S transition, increased cell death in response to CDDP treatment, and decreased the colony formation of A549 cells. MiR-26a significantly decreased the expression of E2F1, diminished Akt phosphorylation, and downregulated Bcl2 expression. Cell growth was suppressed by inhibiting HMGA2-mediated E2F1-Akt pathway.Conclusion: MiR-26a is responsible for A549 cell sensitivity in the treatment of CDDP through regulating HMGA2-mediated E2F1-Akt pathway.

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Section: Introductionmentioning

confidence: 99%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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“…On the other hand, the biological role of miR-15b/16-2 is still controversial, as this cluster has been reported to behave as either a tumor suppressor [acute promyelocytic leukemia (8,9) and osteosarcoma (10)] or an oncogene [melanoma (11), upregulated in the plasma of colorectal cancer (12) and head and neck carcinoma (13)]. …”

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confidence: 99%

miR-15b/16-2 deletion promotes B-cell malignancies

Lovat

Fassan

Gasparini

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

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The central role of the microRNA (miR) 15a/16-1 cluster in B-cell oncogenesis has been extensively demonstrated, with over twothirds of B-cell chronic lymphocytic leukemia characterized by the deletion of the miR-15a/16-1 locus at 13q14. Despite the wellestablished understanding of the molecular mechanisms occurring during miR-15a/16-1 dysregulation, the oncogenic role of other miR-15/16 family members, such as the miR-15b/16-2 cluster (3q25), is still far from being elucidated. Whereas miR-15a is highly similar to miR-15b, miR-16-1 is identical to miR-16-2; thus, it could be speculated that both clusters control a similar set of target genes and may have overlapping functions. However, the biological role of miR-15b/16-2 is still controversial. We generated miR-15b/16-2 knockout mice to better understand the cluster's role in vivo. These mice developed B-cell malignancy by age 15-18 mo with a penetrance of 60%. At this stage, mice showed significantly enlarged spleens with abnormal B cell-derived white pulp enlargement. Flow cytometric analysis demonstrated an expanded CD19+ CD5+ population in the spleen of 40% knockout mice, a characteristic of the chronic lymphocytic leukemia-associated phenotype found in humans. Of note, miR-15b/16-2 modulates the CCND2 (Cyclin D2), CCND1 (Cyclin D1), and IGF1R (insulin-like growth factor 1 receptor) genes involved in proliferation and antiapoptotic pathways in mouse B cells. These results are the first, to our knowledge, to suggest an important role of miR-15b/16-2 loss in the pathogenesis of B-cell chronic lymphocytic leukemia.miRNAs | miR-15b | chronic lymphocytic leukemia | B cells | murine models M icroRNAs (miRNAs) are a class of small noncoding RNAs that modulate gene expression in many physiological and pathological conditions (1). Altered miRNA expression has been reported in several human cancers, and miRNA expression profiles vary according to the considered tumor (2).A role for miRNAs in tumorigenesis and progression was originally documented for the miR-15/16 family (2-5). This group of miRNAs encompasses the miR-15a/16-1 cluster (on chromosome 13q14,) the miR-15b/16-2 cluster (on chromosome 3q25), and the miR-195/497 cluster (on chromosome 17p13).The role of the miR-15a/16-1 cluster in B-cell pathology has been extensively demonstrated (5). The deletion of the miR-15a/ 16-1 cluster has been reported in over two-thirds of B-cell chronic lymphocytic leukemias (B-CLLs) (5). Our group has demonstrated that the loss of miR-15a/16-1 expression induces higher levels of the antiapoptotic proteins BCL2 and myeloid cell leukemia sequence 1 (BCL2-related) (MCL1) (3, 6). Moreover, this deletion promotes mature B-cell expansion by deregulating the transition from G1 to S phase (7).On the other hand, the biological role of miR-15b/16-2 is still controversial, as this cluster has been reported to behave as either a tumor suppressor [acute promyelocytic leukemia (8, 9) and osteosarcoma (10)] or an oncogene [melanoma (11), upregulated in the plasma of colorectal cancer (12) and...

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“…Xia et al (34) identified that miR-15 may enhance the sensitivity of gastric cancer cells to anticancer drugs by targeting BCL2 and promoting apoptosis. Reduced levels of miR-15 are also associated with chemotherapeutic resistance in human tongue cancer cells by targeting BMI1 (14). However, it has also been identified that increased expression of miR-15 is associated with decreased sensitivity to cisplatin and the poor prognosis of patients with lung adenocarcinoma by suppressing the expression of phosphatidylethanolamine-binding protein 4 (13).…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have suggested that miR-15 functions as an oncogene, whereas others regard it as a tumour suppressor (11,12). The effects of miR-15 on chemotherapy are also inconsistent (13,14) and to the best of our knowledge, there have been no studies investigating the potential effect of miR-15 on colon cancer chemotherapy.…”

Section: Introductionmentioning

confidence: 89%

Overexpression of microRNA-15 increases the chemosensitivity of colon cancer cells to 5-fluorouracil and oxaliplatin by inhibiting the nuclear factor-κB signalling pathway and inducing apoptosis

et al. 2017

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Abstract. Overcoming chemoresistance is a challenge in clinical treatment. It has been reported that microRNAs (miRNAs) are involved in regulating chemosensitivity. Therefore, the present study aimed to identify the effect and mechanism of miR-15 on colon cancer chemotherapy. Reverse transcription-quantitative polymerase chain reaction was performed to measure miR-15 level sin62-paired colon cancer and para-cancerous colon tissues. The overexpression of miR-15 in HCT116 cells was induced by transfection. The effect of miR-15 on the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU) and Oxaliplatin (OX) was determined using a luminescent cell viability assay. Flow cytometry, dual-luciferase assay and western blot analysis were used to determine the potential mechanism of miR-15. The results suggested that the expression of miR-15 was decreased in tumour tissues and that overexpression of miR-15 increased the chemosensitivity of colon cancer cells to 5-Fu and OX. miR-15 promoted apoptosis in colon cancer cells treated with 5-Fu and OX by inhibiting the expression of p50, which repressed the expression of B cell lymphoma-2 and B cell lymphoma-extra large; two direct target genes of nuclear factor-κB with anti-apoptotic functions. Thus, the current study demonstrated that miR-15 increased the chemosensitivity of colon cancer cells to 5-FU and OX by inhibiting the NF-κB signalling pathway and inducing apoptosis.

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MiR-200b and miR-15b regulate chemotherapy-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting BMI1

Cited by 225 publications

References 43 publications

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

miR-15b/16-2 deletion promotes B-cell malignancies

Overexpression of microRNA-15 increases the chemosensitivity of colon cancer cells to 5-fluorouracil and oxaliplatin by inhibiting the nuclear factor-κB signalling pathway and inducing apoptosis

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