miR‐10b expression in breast cancer stem cells supports self‐renewal through negative <scp>PTEN</scp> regulation and sustained <scp>AKT</scp> activation

Bahena, Iván; Espinosa, Magali; Ceballos‐Cancino, Gisela; Lizárraga, Floria; Campos‐Arroyo, Denise; Schwarz, Angela; Garcia‐Lopez, Patricia; Maldonado, Vilma; Meléndez-Zajgla, Jorge

doi:10.15252/embr.201642700

Cited by 36 publications

(25 citation statements)

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“…Conversely, miR-10b-5p, a “metastamiR” correlated with the cancer stem cell (CSC) phenotype (Bahena-Ocampo et al, 2016), was one of the few miRNAs significantly downregulated in MMTV-induced tumors. Unlike miR-19a-3p, miR-20a-5p, miR-17a-5p, miR-183a-5p, miR-93-5p, and miR-429-3p, which were upregulated in all infected lactating and mammary tumor tissues, decreased miR-10b-5p levels were only observed in the tumor tissue (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

MMTV does not encode viral microRNAs but alters the levels of cancer-associated host microRNAs

et al. 2018

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Mouse mammary tumor virus (MMTV) induces breast cancer in mice in the absence of known virally-encoded oncogenes. Tumorigenesis by MMTV is thought to occur primarily through insertional mutagenesis, leading to the activation of cellular proto-oncogenes and outgrowth of selected cells. Here we investigated whether MMTV encodes microRNAs (miRNAs) and/or modulates host miRNAs that could contribute to tumorigenesis. High throughput small RNA sequencing analysis of MMTV-infected cells and MMTV-induced mammary tumors demonstrates that MMTV does not encode miRNAs. However, infected tissues have altered levels of several host miRNAs, including increased expression of members of the oncogenic miRNA cluster, miR-17-92. Notably, similar changes in miRNA levels have been previously reported in human breast cancers. Combined, our results demonstrate that virally encoded miRNAs do not contribute to MMTV-mediated tumorigenesis, but that changes in specific host miRNAs in infected cells may contribute to virus replication and tumor biology.

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Section: Discussionmentioning

confidence: 99%

MMTV does not encode viral microRNAs but alters the levels of cancer-associated host microRNAs

et al. 2018

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“…miR-10b expression has been found to be preferentially up-regulated in basal-like/triple-negative breast cancer cell lines and in advanced/metastatic breast cancers (52,53). Recently, miR-10b was shown to be overexpressed in breast cancer stem cells (BCSCs) and to be required for self-renewal of BCSCs (54). The oncogenic role of miR-10b in BCSCs is found to result from its inhibitory effect on PTEN expression, leading to activation of the oncogenic PI3K/AKT pathway (54).…”

Section: Discussionmentioning

confidence: 99%

Tumor-associated myoepithelial cells promote the invasive progression of ductal carcinoma in situ through activation of TGFβ signaling

Zhang

Yao

et al. 2017

Journal of Biological Chemistry

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The normal myoepithelium has a tumor-suppressing nature and inhibits the progression of ductal carcinoma (DCIS) into invasive ductal carcinoma (IDC). Conversely, a growing number of studies have shown that tumor-associated myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of tumor-associated myoepithelial cells in the DCIS-to-IDC development remains undefined. To address this, we explored the role of tumor-associated myoepithelial cells in the DCIS-to-IDC progression. We developed a direct coculture system to study the cell-cell interactions between DCIS cells and tumor-associated myoepithelial cells. Coculture studies indicated that tumor-associated myoepithelial cells promoted the invasive progression of a DCIS cell model, and mechanistic studies revealed that the interaction with DCIS cells stimulated tumor-associated myoepithelial cells to secrete TGFβ1, which subsequently contributed to activating the TGFβ/Smads pathway in DCIS cells. We noted that activation of the TGFβ signaling pathway promoted the epithelial-mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS cells. Importantly, xenograft studies further demonstrated that tumor-associated myoepithelial cells enhanced the DCIS-to-IDC progression Furthermore, we found that TGFβ-mediated induction of oncogenic miR-10b-5p expression and down-regulation of, a miR-10b-5p-targeted tumor-suppressor gene, contributed to the invasive progression of DCIS. Our findings provide the first experimental evidence to directly support the paradigm that altered DCIS-associated myoepithelial cells promote the invasive progression of DCIS into IDC via TGFβ signaling activation.

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“…PTEN is a tumor suppressor gene that has an important regulatory role in cell proliferation and apoptosis (18). PTEN is the target gene of miR-10b (19). Western blot analysis demonstrated that miR-10b mimic inhibited PTEN expression in tumor cells and miR-10b inhibitor promoted PTEN expression (Fig.…”

Section: Mir-10b Regulates the Expression Of Tgf-β And Ptenmentioning

confidence: 99%

Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

Liu

Salai

et al. 2019

Exp Ther Med

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MicroRNA (miR)-10b is highly expressed in esophageal cancer tissues and is associated with poor prognosis of esophageal cancer. However, the role and mechanism of miR-10b in esophageal cancer cells remains unclear, therefore, the present study aimed to investigate this. Esophageal cancer cells, TE-1 and EC9706, were transfected with miR-10b mimic, miR-10b inhibitor or incubated with transforming growth factor-β (TGF-β). MTT and EdU assays were used to detect cell proliferation. Flow cytometry was used to determine cell cycle analysis and apoptosis. Cell migration and invasion were also analyzed. Western blot analysis was used to detect protein levels and reverse transcription-quantitative PCR was used to analyze miR-10b expression. The present results demonstrated that, compared with the control group, miR-10b significantly promoted TE-1 and EC9706 cell proliferation. Compared with miR-10b inhibitor group and control group, miR-10b mimic promoted esophageal cancer cell cycle progression, inhibited apoptosis of esophageal cancer cells and promoted the migration and invasion of cells. The proliferation of esophageal cancer cells increased in a dose-dependent manner with TGF-β concentration. TGF-β treatment induced high expression of miR-10b in both cell lines. The miR-10b mimic + TGF-β group further promoted the migration and invasion of esophageal cancer cells. Western blot analysis determined that, compared with the control group, miR-10b mimic increased TGF-β expression. miR-10b mimic also inhibited the expression of phosphatase and tensin homolog (PTEN) in tumor cells. Compared with the control group, TGF-β inhibited the expression of PTEN with the miR-10b mimic + TGF-β group further inhibiting the PTEN. miR-10b inhibitor + TGF-β reversed the effect of TGF-β and miR-10b on PTEN. In conclusion, miR-10b promoted cell cycle progression, inhibited apoptosis and promoted the migration and invasion of esophageal cancer cells. The mechanism may be related to the upregulation of TGF-β and the downregulation of PTEN. The present findings suggested that miR-10b might be a potential therapeutic target for esophageal cancer.

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miR‐10b expression in breast cancer stem cells supports self‐renewal through negative PTEN regulation and sustained AKT activation

Cited by 36 publications

References 0 publications

MMTV does not encode viral microRNAs but alters the levels of cancer-associated host microRNAs

MMTV does not encode viral microRNAs but alters the levels of cancer-associated host microRNAs

Tumor-associated myoepithelial cells promote the invasive progression of ductal carcinoma in situ through activation of TGFβ signaling

Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

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