miR-15a/miR-16 down-regulates BMI1, impacting Ub-H2A mediated DNA repair and breast cancer cell sensitivity to doxorubicin

Patel, Nibedita; Garikapati, Koteswara Rao; Pandita, Raj K.; Singh, Dharmendra Kumar; Pandita, Tej K.; Bhadra, Utpal; Bhadra, Manika Pal

doi:10.1038/s41598-017-02800-2

Cited by 42 publications

(26 citation statements)

References 58 publications

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“…miR‐16 directly targets BMI‐1, which is a repressor of p16 INK4A and p19 INK4D cell cycle inhibitors . Another study reported that miR‐16 induces G2/M arrest through suppression of BMI1 in MDA‐MB‐231 cells . Considering the inhibitory effect of miR‐302 cluster on BMI‐1, it can be expected that transfection with miR‐16 may enhance this effect and lead to a stronger cell cycle arrest as we detected.…”

Section: Discussionsupporting

confidence: 65%

“…62,63 Another study reported that miR-16 induces G2/M arrest through suppression of BMI1 in MDA-MB-231 cells. 64 Considering the inhibitory effect of miR-302 cluster on BMI-1, 12 it can be expected that transfection with miR-16 may enhance this effect and lead to a stronger cell cycle arrest as we detected. In both MDA-miR-302/367 and SK-miR-302/367 cells, transfection with miR-16 mimic led to CDKN1A overexpression.…”

Section: Discussionmentioning

confidence: 56%

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miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

2020

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Overexpression of either miR‐302 or miR‐302/367 cluster induces reprogramming of cancer cells and exerts tumor‐suppressive effects by induction of mesenchymal‐to‐epithelial transition, apoptosis and a less proliferative capacity. Several reports have described miR‐16 as a tumor suppressor microRNA (miRNA). Here, we studied the impact of exogenous induction of miR‐16 in MDA‐MB‐231 and SK‐BR‐3 breast cancer cells following overexpression of miR‐302/367 cluster and investigated whether transfection of these cells by a mature miR‐16 mimic could affect the reprogramming state of the cells and their tumorigenicity. miR‐16 enhanced the expression levels of OCT4A, SOX2, and NANOG, generally known as transcription or pluripotency factors, and suppressed proliferation and invasiveness of these cells. Meanwhile, inhibition of miR‐16 counteracted both the reprogramming effect and the antitumor function of miR‐302/367 in the breast cancer cells. Current results indicate that miR‐16 can work as an adjuvant to improve both cancer cell reprogramming and tumor‐suppressive function of miR‐302/367 cluster in MDA‐MB‐231 and SK‐BR‐3 cells, while its inhibition counteracts all of these effects. Combined application of miRNAs that share some common targets in cancer cell signaling pathways may provide new approaches for repression of multiple hallmarks of cancer.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 56%

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

2020

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“…In addition, miR‐195 , a member of the miR‐15/miR‐16 family, has been shown to inhibit glioma cell proliferation and to modulate acquired resistance to TMZ . Moreover, members of the miR‐15/miR‐16 family have been linked to resistance against other drugs, including cisplatin, doxorubicin and 5‐fluorouracil . Therefore, we addressed potential effects of miR‐16‐5p overexpression on the response of glioma cells to irradiation and TMZ.…”

Section: Discussionmentioning

confidence: 99%

MiR‐16‐5p is frequently down‐regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis and response to cytotoxic therapy

Krell

Wolter

Stojcheva

et al. 2019

Neuropathology Appl Neurobio

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Aims Aberrant expression of microRNAs (miRNAs) is frequent in various cancers including gliomas. We aimed to characterize the role of miR‐16‐5p as a candidate tumour suppressor miRNA in gliomas. Methods Real‐time PCR‐based approaches were used for miRNA and mRNA expression profiling of glioma and non‐neoplastic brain tissues as well as glioma cell lines. Protein levels were determined by Western blotting. In vitro analyses were performed following overexpression of miR‐16‐5p, trichostatin A (TSA) treatment, and siRNA‐mediated knock‐down of HDAC3 in glioma cells. Effects of miR‐16‐5p on glioma cell viability, apoptosis and response to irradiation and temozolomide (TMZ) were assessed. Results Expression of miR‐16‐5p was reduced relative to control brain tissue in isocitrate dehydrogenase (IDH)‐mutant astrocytomas of World Health Organization (WHO) grades II, III and IV, and a subset of IDH‐wildtype glioblastomas WHO grade IV. MiR‐16‐5p expression was lower in IDH‐mutant than in IDH‐wildtype gliomas, and down‐regulated in IDH‐wildtype glioma lines. MiR‐16‐5p overexpression reduced expression of important cell cycle and apoptosis regulators in glioma cells, including CDK6, CDC25A, CCND3, CCNE1, WEE1, CHEK1, BCL2 and MCL1. In line, CDK6, WEE1, CHEK1, BCL2 and MCL1 transcript levels were increased in WHO grade III or IV gliomas. TSA treatment and HDAC3 knockdown in glioma cells induced miR‐16‐5p up‐regulation and reduced expression of its targets. Moreover, miR‐16‐5p overexpression inhibited proliferation and induced apoptosis in various glioma cell lines and increased sensitivity of A172 glioma cells to irradiation and TMZ. Conclusion Reduced expression of miR‐16‐5p contributes to glioma cell proliferation, survival and resistance to cytotoxic therapy.

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“…Previous studies have demonstrated the pivotal role of miRNAs in cancer initiation, progression, and metastasis . miR‐34a and miR‐16 are two tumor suppressor miRNAs associated with the development of breast cancer (BC) …”

Section: Introductionmentioning

confidence: 99%

Suppressive effect of exogenous miR‐16 and miR‐34a on tumorigenesis of breast cancer cells

Haghi

Taha

Javeri

2019

J of Cellular Biochemistry

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Recent investigations have shown tumor-suppressive roles for miR-16 and miR-34a. They also share some features in regard to targeting cancer cell signaling pathways which they control. Therefore, in this study, we aimed to further scrutinize whether exogenous induction of mature miR-34a and miR-16 can collaborate in breast tumor suppression. MDA-MB-231 and SK-BR-3 human breast cancer cell lines were cultured and transfected twice with hsa-miR-16-5p and hsa-miR-34a-5p mimics individually or in combination. The cells were analyzed for apoptosis rate and cell cycle indices by flow cytometry.Also, the expression of several invasion and the epithelial-mesenchymal transition markers was evaluated at gene and protein levels by quantitative real-time polymerase chain reaction and western blot analysis, respectively.Assessment of invasiveness and migratory potential of the transfected cells was performed using three-dimensional spheroid formation and wound-healing assay, respectively. In both cell lines, miR-16 and miR-34a induced apoptosis and cell-cycle arrest and also suppressed invasion and migration. Some of these effects, like cell-cycle arrest and induction of apoptosis, were significantly higher when using both microRNAs than when using them individually for transfection of the cells. Our results are indicating that miR-16 and miR-34a can collaborate in breast tumor suppression. K E Y W O R D Sapoptosis, breast cancer, invasion, miR-16, miR-34a

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miR-15a/miR-16 down-regulates BMI1, impacting Ub-H2A mediated DNA repair and breast cancer cell sensitivity to doxorubicin

Cited by 42 publications

References 58 publications

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

MiR‐16‐5p is frequently down‐regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis and response to cytotoxic therapy

Suppressive effect of exogenous miR‐16 and miR‐34a on tumorigenesis of breast cancer cells

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