RETRACTED: miR-221/222 enhance the tumorigenicity of human breast cancer stem cells via modulation of PTEN/Akt pathway

Li, Bailong; Lü, Ying; Wang, Honghai; Han, Xiaocui; Murata, Jun; Li, Jiazhi; Yu, Lihui; Wang, Bo; Fan, Shujun; Yu, Xiaotang; Song, Bo

doi:10.1016/j.biopha.2016.01.045

Cited by 87 publications

(62 citation statements)

References 37 publications

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“…In human umbilical vein endothelial cells, miR-221 is found to inhibit autophagy by modulating a PTEN/Akt signaling pathway (12). miR-221 targeting PTEN/Akt is also reported in several cancer cells during cancer development (33)(34)(35). Our results implicated a potential role of TP53INP1 on the effect of miR-221 on autophagy of CRC.…”

Section: Discussionsupporting

confidence: 63%

miR‑221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells

Liao¹,

Li²,

Ye³

et al. 2017

Exp Ther Med

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Abstract. Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-associated mortalities worldwide. MicroRNAs (miRNAs/miRs) serve important roles in tumor development, progression and metastasis. miR-221 has been reported to modulate proliferation, apoptosis, cell cycle distribution and cell migration in a variety of cancers. However, the function of miR-221 in the autophagy of cancer is unclear. In the present study, the role of miR-221 in the autophagy of CRC cells was investigated and its associated target was identified. Survival analysis using The Cancer Genome Atlas data suggested that a higher expression of miR-221 was associated with poor survival in patients with CRC. A Cell Counting kit-8 assay revealed that miR-221 promoted CRC cell proliferation. Autophagy flux analyzed by microtubule-associated protein 1 light chain 3 (LC3) turnover indicated that miR-221 reduced autophagy in CRC cells using different protease inhibitors (E64d and pepstatin A; Bafilomycin A1) in nutrient-rich medium or under starvation conditions. Tumor protein 53-induced nuclear protein 1 (TP53INP1) was identified as a potential novel target of miR-221 by bioinformative prediction. The protein expression of TP53INP1 was inversely regulated by miR-221 in CRC cells. Furthermore, luciferase activity assays were performed and indicated that miR-221 may regulate the luciferase activity of wild-type TP53INP1 without interfering with the activity of mutant TP53INP1. These data suggested that miR-221 may promote the cell proliferation of CRC via the inhibition of autophagy and targeted TP53INP1. IntroductionColorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-associated death worldwide (1). The morbidity rates of CRC are increasing substantially in a number of countries within Eastern Asia and Eastern Europe which were previously at low risk (2). The multifactorial etiology of CRC involves lifestyle and dietary factors, such as smoking, red and processed meat consumption, and excessive alcohol consumption (3). Autophagy is a vital transformational switch among mechanisms that are involved in the pathogenesis of CRC (4). Autophagy may act as a suppressor during early stages and as a promoter during advanced stages of CRC (4,5). It is important to determine the regulative mechanisms of autophagy in CRC.Recent studies suggests that the post-transcription and translation regulation mediated by microRNAs (miRNAs/miRs) contribute significantly to autophagy in cancer (6). It is found that miR-23b-3p inhibits autophagy in gastric cancer cells (7) and miR-26 suppresses autophagy in hepatocellular carcinoma cells (8). Whereas miR-193b is suggested to induce autophagy in oesophageal cancer cells (9). It is interesting that different miRNAs play diverse roles in the regulation of autophagy through various targets.

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Section: Discussionsupporting

confidence: 63%

miR‑221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells

Liao¹,

Li²,

Ye³

et al. 2017

Exp Ther Med

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“…log 2 fold change is calculated by comparing test samples (TBL20-EV) to calibrator samples (BL20-EV) using the constitutively expressed miRNA bta-miR-30e-3p as an internal normaliser TABLE 1 Host miRNA differentially expressed in TBL20-EV compared with BL20-EV microRNA Log 2 (p value) Function bta-miR-222 1.63 (p = 1.5E-05) Oncogene in many human malignancies (Felicetti et al, 2016;Kara et al, 2015;Li et al, 2016;M. log 2 fold change is calculated by comparing test samples (TBL20-EV) to calibrator samples (BL20-EV) using the constitutively expressed miRNA bta-miR-30e-3p as an internal normaliser TABLE 1 Host miRNA differentially expressed in TBL20-EV compared with BL20-EV microRNA Log 2 (p value) Function bta-miR-222 1.63 (p = 1.5E-05) Oncogene in many human malignancies (Felicetti et al, 2016;Kara et al, 2015;Li et al, 2016;M.…”

Section: Computational Analysis Of Bta-mir-181a and B Mrna Targetsmentioning

confidence: 99%

Characterisation of infection associated microRNA and protein cargo in extracellular vesicles ofTheileria annulatainfected leukocytes

Gillan

Simpson

Kinnaird

et al. 2018

Cellular Microbiology

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The protozoan parasites Theileria annulata and Theileria parva are unique amongst intracellular eukaryotic pathogens as they induce a transformation‐like phenotype in their bovine host cell. T. annulata causes tropical theileriosis, which is frequently fatal, with infected leukocytes becoming metastatic and forming foci in multiple organs resulting in destruction of the lymphoid system. Exosomes, a subset of extracellular vesicles (EV), are critical in metastatic progression in many cancers. Here, we characterised the cargo of EV from a control bovine lymphosarcoma cell line (BL20) and BL20 infected with T. annulata (TBL20) by comparative mass spectrometry and microRNA (miRNA) profiling (data available via ProteomeXchange, identifier PXD010713 and NCBI GEO, accession number GSE118456, respectively). Ingenuity pathway analysis that many infection‐associated proteins essential to migration and extracellular matrix digestion were upregulated in EV from TBL20 cells compared with BL20 controls. An altered repertoire of host miRNA, many with known roles in tumour and/or infection biology, was also observed. Focusing on the tumour suppressor miRNA, bta‐miR‐181a and bta‐miR‐181b, we identified putative messenger RNA targets and confirmed the interaction of bta‐miR181a with ICAM‐1. We propose that EV and their miRNA cargo play an important role in the manipulation of the host cell phenotype and the pathobiology of Theileria infection.

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“…Recent work predicted targets of miR-9 and defined their functions, such as EMT induction by targeting the CDH1 mRNA [33,34], mediation of temozolomide resistance of glioblastoma multiforme cells [35,36], and SP expansion and metastasis through loss of α-catenin in squamous cell carcinoma [32]. Moreover, epigenetic modulation of miR-221 contributes to stemness by decreasing DNMT3b expression and promotes cell outgrowth and invasiveness of human breast cancer stem cells via downregulation of PTEN and Trichorhinophalangeal syndrome type 1 (TRPS1) [16,37,38]. Our present results demonstrate that induction of miR-9/221 promotes the generation of cancer stem cell-like cells and help explain the heterogeneity of the invasion/dissemination capacity of SP cells present in breast cancer niches.…”

Section: Discussionmentioning

confidence: 99%

Increased Cellular Levels of MicroRNA-9 and MicroRNA-221 Correlate with Cancer Stemness and Predict Poor Outcome in Human Breast Cancer

Cheng

Hsieh

et al. 2018

Cell Physiol Biochem

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Background /Aims: Recent studies of microRNA (miRNA) involvement in tumorigenesis have indicated the critical role of these non-coding small RNAs in malignant transformation, but the prognostic role, if any, of miRNAs in breast cancer remains undetermined. Therefore, we assessed the prognostic significance of microRNA-9 (miR-9) and miR-221 in breast cancer toward the goal of understanding the contribution(s) of these miRNAs to cancer cell stemness. Methods: The level of each of miR-9 and miR-221 in 206 paired laser capture microdissected tumor cells and non-tumor cells was determined by quantitative reverse transcription-PCR (qRT-PCR). The relationship between the miRNA signature and clinicopathological data and prognosis of breast cancer was assessed. Identification of a stem cell-enriched side population was achieved with fluorescence-activated cell sorting and a sphere-forming assay. Wound healing, Boyden chamber assays, and western blotting were used to study the contribution of each miRNA to tumor cell migration and invasion. Results: We found that induction of miR-9 and miR-221 mimics conferred side-population cells to form spheroidal tumor colonies in suspension culture that maintained the mesenchymal stem-cell potential in non-invasive MCF-7 breast cancer cells. In contrast, knockdown of both miR-9 and miR-221 in invasive MDA-MB-231 breast cancer cells dramatically decreased the number of side-population colonies with stem cell-like potency, which reduced the capacity for tumor-cell renewal, invasion, and migration. Clinically, the mean proportion of miR-9- or miR-221-overexpressing cells was significantly greater in tumor cells compared with non-tumor cells (P < 0.05). Increased levels of miR-9 and miR-221 in breast tissue portended a significantly elevated risk of progression to malignancy with respect to larger tumor size, poor differentiation, late-stage evolution, lymph-node metastasis (P < 0.05), and lower overall survival (Ptrend = 0.017; eight-year follow-up). Conclusion: Our findings provide strong evidence that miR-9 and miR-221 can enhance the generation of cancer stem cells to yield an invasive phenotype and that overexpression of these miRNAs predicts a poor outcome for breast cancer patients.

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RETRACTED: miR-221/222 enhance the tumorigenicity of human breast cancer stem cells via modulation of PTEN/Akt pathway

Cited by 87 publications

References 37 publications

miR‑221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells

miR‑221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells

Characterisation of infection associated microRNA and protein cargo in extracellular vesicles ofTheileria annulatainfected leukocytes

Increased Cellular Levels of MicroRNA-9 and MicroRNA-221 Correlate with Cancer Stemness and Predict Poor Outcome in Human Breast Cancer

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