Metformin mediates induction of miR‐708 to inhibit self‐renewal and chemoresistance of breast cancer stem cells through targeting CD47

Tan, Weige; Tang, Hailin; Jiang, Xinhua; Yan, Feng; Huang, Lili; Shi, Dingbo; Li, Laisheng; Huang, Xiaojia; Li, Li

doi:10.1111/jcmm.14462

Cited by 53 publications

(75 citation statements)

References 35 publications

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“…In another study, miR-708 induced repression of the WNT/βcatenin signaling pathway in BCSCs, causing inhibition of selfrenewal and chemoresistance in these cells. miR-708 was shown to directly bind the CD47 gene regulating the expression of this molecule and the tumor-associated macrophage-mediated phagocytosis (162).…”

Section: Impaired Dcs Recruitment: Ccl4 Inhibitionmentioning

confidence: 99%

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

et al. 2019

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WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies.

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Section: Impaired Dcs Recruitment: Ccl4 Inhibitionmentioning

confidence: 99%

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

et al. 2019

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“…12,16 CD44 has multiple spliced isoforms and heavy glycosylation, which is involved in tumor cell migration in prostate cancer 27 and breast cancer. 28 Kim et al found that hepatocellular carcinoma patients with low expression of CD44 expressed a significantly better disease-free survival rate compared to those with higher CD44 29 and found that CD44 expression was an independent factor associated with survival. 30 Lina et al demonstrated that upregulation of CD44 as well as the variant isoforms can promote the activation induced by EGFR downstream signaling pathways.…”

Section: Dovepressmentioning

confidence: 99%

<p>Long Non-Coding RNA LOXL1-AS1 Enhances Colorectal Cancer Proliferation, Migration and Invasion Through miR-708-5p/CD44-EGFR Axis</p>

Cui

Chen

et al. 2020

OTT

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Introduction: Colorectal cancer (CRC), the third most common cancer worldwide, involves a physiological and pathological long non-coding RNA (lncRNA) paradigm shift. It has been reported that the lncRNA LOXL1-AS1 affects tumor development for many kinds of cancers, but its functions and mechanisms in CRC remain unknown. Methods: Expression levels of LOXL1-AS1 and miR-708-5p within CRC tissues and cell lines were measured using qRT-PCR. The performance of gain-of-function and loss-offunction assays was aimed at examining the effects of LOXL1-AS1 and miR-708-5p; colony formation and cell viability assays were carried out to measure cell multiplication; and Transwell migration and wound-healing assays were carried out for the measurement of cell migration and invasion. Luciferase reporter assay was used to verify the interactions between LOXL1-AS1 and miR-708-5p and between miR-708-5p and the CD44-EGFR signaling pathway. Finally, expression of CD44 and EGFR proteins was measured by Western blot and immunofluorescence assays. Results: In this study, we reveal that the regulation of lncRNA LOXL1-AS1 occurs within CRC based on the correlation with poor clinical outcomes. LOXL1-AS1 knockdown along with miR-708-5p overpresentation in CRC cell lines inhibited cell multiplication, migration, and invasion. The inhibiting effect of LOXL1-AS1 knockdown on CRC was reversed by upregulating the CD44-EGFR signal pathway. From the perspective of mechanism, LOXL1-AS1 imposes sponging upon miR-708-5p and thereby promotes the CD44-EGFR signal pathway in CRC cells. Discussion: This study demonstrated that lncRNA LOXL1-AS1 enhances multiplication, migration, invasion, and progression of CRC by sponging miR-708-5p to regulate the CD44-EGFR signal pathway.

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“…Characteristics of included studies are presented in Table 3. All articles were published between 2011 and 2019 and were written in English [33][34][35][36]. Studies have been carried out on two types of cancers: breast cancer [33,34,36] and pancreatic cancer [35].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…All articles were published between 2011 and 2019 and were written in English [33][34][35][36]. Studies have been carried out on two types of cancers: breast cancer [33,34,36] and pancreatic cancer [35]. The studies were conducted in the USA (n = 1) [35], Spain (n = 1) [36], Japan (n = 1) [34] and in China (n = 1) [33].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Studies have been carried out on two types of cancers: breast cancer [33,34,36] and pancreatic cancer [35]. The studies were conducted in the USA (n = 1) [35], Spain (n = 1) [36], Japan (n = 1) [34] and in China (n = 1) [33]. All four studies were performed in vitro [33][34][35][36], three of them also involved in vivo studies on animals (female BALB/c nude mice [33]; female NON/SCID mice [34]; female CB17/SCID mice [35]).…”

Section: Study Characteristicsmentioning

confidence: 99%

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Metformin’s Modulatory Effects on miRNAs Function in Cancer Stem Cells—A Systematic Review

Malinowski

Musiała

Wiciński

2020

Cells

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Cancer stem cells (CSCs) have been reported in various hematopoietic and solid tumors, therefore, are considered to promote cancer progression, metastasis, recurrence and drug resistance. However, regulation of CSCs at the molecular level is not fully understood. microRNAs (miRNAs) have been identified as key regulators of CSCs by modulating their major functions: self-renewal capacity, invasion, migration and proliferation. Various studies suggest that metformin, an anti-diabetic drug, has an anti-tumor activity but its precise mechanism of action has not been understood. The present article was written in accordance to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We systematically reviewed evidence for metformin’s ability to eradicate CSCs through modulating the expression of miRNAs in various solid tumors. PubMed and MEDLINE were searched from January 1990 to January 2020 for in vitro studies. Two authors independently selected and reviewed articles according to predefined eligibility criteria and assessed risk of bias of included studies. Four papers met the inclusion criteria and presented low risk bias. All of the included studies reported a suppression of CSCs’ major function after metformin dosage. Moreover, it was showed that metformin anti-tumor mechanism of action is based on regulation of miRNAs expression. Metformin inhibited cell survival, clonogenicity, wound-healing capacity, sphere formation and promotes chemosensitivity of tumor cells. Due to the small number of publications, aforementioned evidences are limited but may be consider as background for clinical studies.

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Metformin mediates induction of miR‐708 to inhibit self‐renewal and chemoresistance of breast cancer stem cells through targeting CD47

Cited by 53 publications

References 35 publications

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

<p>Long Non-Coding RNA LOXL1-AS1 Enhances Colorectal Cancer Proliferation, Migration and Invasion Through miR-708-5p/CD44-EGFR Axis</p>

Metformin’s Modulatory Effects on miRNAs Function in Cancer Stem Cells—A Systematic Review

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