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Background: Breast cancer is the most common type of cancer among women, and despite improved treatments, it remains a major challenge. However, improved mechanistic insight may lead to novel therapeutic strategies. miR‐142‐3p belongs to the miR‐142 family and is involved in pathogenesis and metastasis of various types of malignancies by targeting several important messenger RNAs (mRNAs) including Bach‐1. This is especially true for breast cancer, where Bach‐1 is involved in the metastatic spread by deregulation of metastasis‐associated genes. Methods: In this study, we collected 24 breast cancer tissues with 24 adjusted normal tissues to measure the expression levels of miR‐142‐3p and Bach‐1 mRNA using quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and IHC. miR‐142‐3p targeting of Bach‐1 expression in MCF‐7 and MDA‐MB‐468 breast cancer cells was evaluated using bioinformatics, qRT‐PCR and western blot analyses. The cellular proliferation, invasion, and migration were assessed by MTT, transwell matrigel and wound healing assay and the EMT‐associated proteins C‐X‐C chemokine receptor type 4 (CXCR‐4), matrix metalloproteinase‐9 (MMP9), and vascular endothelial growth factor receptor (VEGFR) were analyzed by western blot analysis. Also, the expression levels of tumor suppressors including miR‐330, miR‐145, and miR‐34a were estimated by qRT‐PCR. Results: Analysis of paired specimens of primary malignant and normal tissues showed that miR‐142‐3p was downregulated, while Bach‐1 mRNA and protein both were overexpressed in the breast cancer tumors. This inverse relationship was confirmed by cell line experiments demonstrating that miR‐142‐3p expression reduced Bach‐1 mRNA levels. Furthermore, replacement of miR‐142‐3p could inhibit the proliferation, invasion, and migration in breast cancer potentially by targeting of Bach‐1 mRNA and subsequent inhibition of CXCR4, MMP9, and VEGFR protein expressions. In addition, induction of miR‐142‐3p could upregulate tumor suppressor miRNAs, including miR‐330, miR‐145, and miR34a. Conclusion: For the first time, our results revealed that miR‐142‐3p could target Bach‐1in breast cancer cells leading to the reduction of EMT‐related proteins and reduced cell proliferation, invasion, and migration. The results also demonstrated that miR‐142‐3p could regulate important tumor suppressor miRNAs in breast cancer cells. In conclusion, our results suggest that miR‐142‐3p could be a good candidate for the targeted therapy of breast cancer, especially for the invasive type. Our results revealed that miR‐142‐3p could target Bach‐1in breast cancer cells leading to the reduction of EMT‐related proteins and reduced cell proliferation, invasion, and migration. The results also demonstrated that miR‐142‐3p could regulate important tumor suppressor miRNAs in breast cancer cells. The results suggest that miR‐142‐3p could be a good candidate for the targeted therapy of breast cancer, especially for the invasive type. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PC) is one of the most prevalent types of malignancies in males. Here, we replaced the miRNA-143 in PC cells by using a vector-based miRNA-143 transfection approach. Materials and methods: The miRNA-143 vector was transfected into the cells and qRT-PCR was applied to assess the expression of target genes in PC3 cells. Also, the MTT, scratch wound-healing, and DAPI staining assays were done to assess the proliferation, migration, and apoptosis of the cells, respectively. Results: The findings of the qRT-PCR determined the enhanced expression of miRNA-143 and other cancer-associated genes. The MTT and wound-healing assays revealed the proliferation and migration reduction in the transfected cells in comparison to control cells that contain an empty vector. Conclusion: The miRNA-143 has a significant impact on cell growth and migration during PC metastasis, and it may be a promising candidate for molecular therapies of PC. [ABSTRACT FROM AUTHOR]

Abstract MicroRNAs are post-transcriptional mediators of gene expression and regulation, which play influential roles in tumorigenesis and cancer metastasis. The expression of tumor suppressor miR-145 is reduced in various cancer cell lines, containing both solid tumors and blood malignancies. However, the responsible mechanisms of its down-regulation are a complicated network. miR-145 is potentially able to inhbit tumor cell metastasis by targeting of multiple oncogenes, including MUC1, FSCN1, Vimentin, Cadherin, Fibronectin, Metadherin, GOLM1, ARF6, SMAD3, MMP11, Snail1, ZEB1/2, HIF-1α and Rock-1. This distinctive role of miR-145 in the regulation of metastasis-related gene expression may introduce miR-145 as an ideal candidate for controlling of cancer metastasis by miRNA replacement therapy. The present review aims to discuss the current understanding of the different aspects of molecular mechanisms of miR-145 regulation as well as its role in r metastasis regulation. [ABSTRACT FROM AUTHOR]

Gastric cancer is responsible for approximately one million annual deaths worldwide. Recently, the important roles of miRNAs as vital factors in malignancy processes such as metastasis have identified. They involve in the regulation of different biological procedures such as proliferation, invasion, metastasis and cell survival. MiR-146a has an aberrant expression in different tumors and has different expressions in the gastric cancer cell lines. This microRNA can act as a tumor suppressor and/or oncogene in gastric cancer related cases. Most of the studies have confirmed that miR-146a is downregulated in human gastric cancer cell lines and tissues, significantly and that it has tumor suppressor effects in gastric cancers. On the other hand, the role of miR-146a as an oncogene has been studied in an in-vitro experiment and results showed that over- an expression of miR-146a in gastric cancer tissues inhibits apoptosis and improves cell proliferation of gastric cancer cell. MiR-146a also has been a candidate for diagnosis and prognosis in gastric cancer cases. In this review, we focus on the important roles of miR-146a in tumor genesis of gastric tissues, emphasizing on the involvement of this microRNA in diagnosis, prognosis, chemotherapy response and finally, potential therapeutic applications as an anticancer agent in inhibition of gastric cancer cell metastasis and invasion. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome. MiRNA-143 is defined as an important tumor suppressor in a variety of neoplasms including solid tumors and B-cell malignancies. MiRNA-143 is involved in the pathogenesis of cancers by directly targeting several mRNAs such as Bcl-2 , KRAS , HK2 , DNMT3A , TP53 and MMP-13 . In this study, an overview of the miRNA-143 function in different signaling pathways in cancer will be provided. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer grows and spreads faster compared to other types of invasive breast cancer and has limited treatment options and subsequently worse prognosis. High mobility group A 2 (HMGA2) protein is widely expressed in undifferentiated cells including cancer cells. HMGA2 is a DNA binding protein involved in DNA architecture and the functional regulation of DNA. It was reported that HMGA2 is aberrantly regulated malignant signaling in different types of cancers. In this study, we aim to reveal the role of HMGA2 in TNBC biology and demonstrate a link between HMGA2-mediated cancer phenotypes and the regulation of NF-kB/IL-6/STAT3 signaling. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that exhibits a high proliferation rate and early metastasis leading to a poor prognosis. HMGA2 is a DNA binding transcriptional regulator implicated in tumorigenesis. Here, we demonstrate that the HMGA2 promoter is demethylated in TNBC tumors, leading to increased expression of HMGA2 at both mRNA and protein levels. Importantly, high HMGA2 levels in TNBC tumors are correlated with poor prognosis. To detail the role of HMGA2 in TNBC development and progression, we studied its effect on core cancer phenotypes. Stable knockdown of HMGA2 in TNBC cells revealed that HMGA2 may support cell proliferation, cell migration and invasion. In addition, HMGA2 knockdown decreased cancer stem cell (CSC) features. Importantly, we found that silencing HMGA2 inhibited NF-kB signaling and lead to decreased expression of the downstream molecules IL-6 and IL-8 and reduced STAT3 pathway activation. Our results demonstrate that HMGA2 supports cancer hallmarks in TNBC and may represent a promising target for TNBC treatment. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common women's malignancy in the world and, for subgroups of patients, treatment outcomes remain poor. Thus, more effective therapeutic strategies are urgently needed. MicroRNAs (miRNAs) have emerged as promising therapeutic tools and targets, as they play significant roles in regulating key cellular processes by suppressing gene expression. However, additive opportunities involving miRNAs have been underexplored. For example, both miR-34a and miR-200c individually suppress the development of different types of cancer, but the cellular effects of their combined actions remain unknown. Here, we show that miR-34a and miR-200c levels are reduced in breast tumors compared to adjacent normal tissues and that this additively predicts poor patient survival. In addition, in cell lines, miR-34a and miR-200c additively induce apoptosis and cell cycle arrest, while also inhibiting proliferation, invasion, migration, stemness and epithelial-to-mesenchymal transition (EMT). Mechanistically, both miRNA-34a and miR-200c directly target HIF1-α and subsequently downregulate VEGFR, MMP9 and CXCR4, although combined miRNA-34a and miR-200c delivery suppresses mouse xenograft tumor development as effectively as individual delivery. We establish a model, supported by in vitro and clinical data, which collectively suggest that the co-delivery of miR-34a and miR-200c represents a promising novel therapeutic strategy for breast cancer patients. [ABSTRACT FROM AUTHOR]

One of the major obstacles in the treatment of cancer is resistance to standard chemotherapeutic drugs. According to the numerous reports, miR‐200c is involved in many cancers, especially gastric cancer, and also miR‐200c has been known as an effective factor in the elimination of chemotherapy resistance. The purpose of this study was to explore the potential function and mechanism of miR‐200c and cisplatin in the inhibition of migration and induction of apoptosis in gastric cancer cells. In this study, first, miR‐200c mimics and LNA‐anti‐miR‐200c were transfected into KATOIII cells. Moreover, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay results revealed that increased miR‐200c expression and cisplatin can more inhibited the proliferation of KATOIII cells. MiR‐200c overexpression inhibited the movement of KATOIII cells in wound healing assay. Subsequently, miR‐200c/cisplatin could suppress colony formation in KATOIII cells. To identify a potential miR‐200c target, we investigated the effect of miR‐200c modulation on RhoE, PTEN, VEGFR, and MMP9 expression levels. Increased miR‐200c expression caused a reduction in VEGFR and MMP9 mRNA and protein, suggesting that VEGFR and MMP9 are targets of miR‐200c. In addition, reverse‐transcription polymerase chain reaction assays showed that RhoE is target gene of miR‐200c and LNA‐anti‐miR‐200c suppressed the expression of PTEN. Flow cytometry and 4′,6‐diamidino‐2‐phenylindole staining analysis indicated that miR‐200c increased the cisplatin‐induced apoptosis which may be associated with suppression of RhoE expression in KATOIII cells, also cell‐cycle analysis showed the arrest of cell‐cycle progression at the G2 phase. These data demonstrated that miR‐200c functioned as a suppressor gene in KATOIII cells. Also, miR‐200c can be a potential therapeutic approach to overcome chemoresistance during cisplatin chemotherapy. [ABSTRACT FROM AUTHOR]

miR‐143 is a tumor suppressor miRNA which its downregulation is frequently reported in colorectal cancer (CRC). This miRNA is a negative regulator of K‐RAS, c‐MYC, BCL‐2, and MMP‐9 genes which are engaged in tumor growth and metastasis. In the present study, miR‐143 restoration was performed by transfection of the pCMV‐miR‐143 vector into the SW‐480 CRC cells. Subsequently, alterations in proliferative and migratory potential of the cells were investigated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and wound‐healing assays, respectively. Moreover, to detect apoptosis incidence in the transfected cells, 4',6‐diamidino‐2‐phenylindole (DAPI) staining was used. Furthermore, mRNA levels of c‐MYC, K‐RAS, MMP‐9, and BCL‐2, as potential targets of miR‐143, were assessed by quantitative Real‐Time PCR (qRT‐PCR). Also the expression levels of c‐MYC, K‐RAS, and MMP‐9 proteins were investigated by the western blot analysis. Finally, the ratio of BAX to BCL‐2 expression, as a potential marker of the response to apoptosis stimuli, was compared between the control and test groups. Furthermore, the trypan blue test was performed to determine the cell viability in cell suspension. According to the results, a decreased viability and migratory potential was observed for the miR‐143 receiving cells. The DAPI staining also confirmed the occurrence of apoptosis. Moreover, BCL‐2, K‐RAS, MMP‐9, and c‐MYC mRNAs were significantly downregulated in the miR‐143 grafted cells. The BAX/BCL‐2 ratio also indicated a notable increase in the cells with miR‐143 overexpression. In brief, miR‐143 replacement could be considered as an effective strategy for the management of CRC and attenuating its invasive features. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate several biological and physiological processes in mammalian cells, including cellular proliferation, differentiation, apoptosis, and metabolism. Recent studies have confirmed the alteration of them during the cancer development. Matrix metalloproteinases (MMPs), belonging to the large family of proteases, have also been demonstrated to play crucial roles in tissue remodeling, and to support cancer progression and metastasis. There are several known miRNAs which regulate the MMP family and their expression. The expression profiles of miRNAs involved in MMP regulation, change during cancer progression, and metastasis. The present review focuses on important miRNAs capable of targeting MMPs through direct and indirect interactions during the breast cancer development, progression, and metastasis. MicroRNAs (miRNAs) regulate several biological and physiological processes in mammalian cells, including cellular proliferation, differentiation, apoptosis, and metabolism. Recent studies have confirmed the alteration of them during the cancer development. Matrix metalloproteinases (MMPs), belonging to the large family of proteases, have also been demonstrated to play crucial roles in tissue remodeling, and to support cancer progression and metastasis. There are several known miRNAs which regulate the MMP family and their expression. The expression profiles of miRNAs involved in MMP regulation, change during cancer progression and metastasis. [ABSTRACT FROM AUTHOR]

Evading immune destruction is a hallmark of cancer. Myeloid‐derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3+ T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA‐DR – CD33 + MDSCs in peripheral blood is about 10‐fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA‐DR – CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient‐derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient‐derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC. Myeloid‐derived suppressor cells (MDSCs) are thought to foster the establishment of an immunosuppressive tumor microenvironment. By being more abundant and more effective T cell suppressors, breast cancer patient‐derived circulating MDSCs exert a dual immunosuppressive effect. Moreover, increased circulating MDSC levels robustly associate with advanced breast cancer stage and positive lymph node status. [ABSTRACT FROM AUTHOR]

Background: Cancer lethality is mainly caused by metastasis. Therefore, understanding the nature of the genes involved in this process has become a priority. BACH1, a basic leucine zipper transcription factor, has been shown to transcriptionally regulate expression of a range of genes that are associated with breast cancer metastasis. However, the exact role and the underlying molecular mechanism of BACH1 in prostate cancer remain unclear. This study aims to explore the expression of BACH1 in prostate cancer tissues and the effect of BACH1 suppression on prostate cancer cell behavior. Materials and methods: In this study, we used quantitative real-time PCR (qRT-PCR) to measure BACH1 expression in prostate adenocarcinoma tissues and two metastasis-derived prostate cancer cell lines, DU145 and LNCaP. We also used immunohistochemical (IHC) staining to measure BACH1 protein expression in prostate adenocarcinoma and matched normal tissue samples. In the following BACH1 expression was silenced in DU145 cells using siRNA as well. Knockdown was confirmed by qRT-PCR and Western blotting. The cytotoxic effects of BACH1-siRNA on DU145 cells were determined using an MTT assay. The migration and invasive capacity of DU145 cells were examined by scratch wound healing assay and matrigel invasion assay, respectively. We also used qRT-PCR to study the effect of BACH1 silencing on the expression levels of metastasis-related genes. Results: We find that the expression of BACH1 mRNA and protein in prostate cancer tissues is significantly higher than in matched normal prostate tissues (p < .05). In addition, DU145 and LNCaP cells exhibited 4.25-fold and 3.45-fold higher levels of BACH1 compared to HFF cell line. BACH1-siRNA significantly reduced both mRNA and protein expression levels in DU145 cells. More importantly, we show that BACH1 promotes key features of metastasis, as BACH1-siRNA treatment significantly reduced cell invasion and migration by changing the expression levels of a number of metastasis-related genes in vitro. Conclusions: BACH1 is overexpressed in prostate cancer. Because this promotes invasion and migration, it may facilitate metastasis of prostate cancer. Thus, BACH1 is a potential therapeutic target for metastatic prostate cancer. BACH1 silencing therapy can be considered as a novel and effective adjuvant in prostate cancer targeted therapies. [ABSTRACT FROM AUTHOR]

Introduction Breast adenocarcinoma is the second common cancer in women the incidence of which is increasing in many countries, especially in developing companies. In this study, miRNA143 has been replaced by vector based microRNA-143 in breast adenocarcinoma cells (MDA-MB-468) and its anti-cancer effects on breast adenocarcinoma cells have been evaluated. Methods The pCMV-MIR-143 vector was transfected into MDA-MB-468 cells via JetPEI transfection reagent. The transfected cells were selected by IC50 concentration of Geneticin antibiotic (G418) after a 2-week treatment. To evaluate the effect of miR-143 on the inhibition of migration, scratch wound healing assay was performed. Then, the expression level of miR-143, Kras, Vimentin, CXCR4, MMP9 and E-Cadherin were measured by the qRT-PCR method. Results Results of MTT and wound healing assays showed that miR-143 inhibited cell growth and cell migration in miR-143 induced cell line compared with control group. The result of gene expression showed that miR-143 reduced Kras, Vimentin, CXCR4 and MMP9 expression, and increased E-Cadherin expression in miR-143 replaced cells compared to control cells. Conclusion The results showed that miRNA-143 plays an important role in cell growth and migration during breast cancer development and metastasis and it can be a candidate as a therapeutic molecule in microRNA replacement therapy of breast adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background Metastasis to distant organs is a hallmark of many tumor cells. BACH1 (BTB and CNC homology 1) is a transcriptional factor which promotes the migration and invasion of breast cancer cells. BACH1 expression and its target genes are intimately associated with the metastasis possibility of clinical samples, and BACH1 reduction leads to meaningful depletion in metastasis. The evaluation of BACH1 role in colon cancer remains elusive. This study seeks to further investigate the role of BACH1 in colon cancer cells. Methods Quantitative RT-PCR (qRT-PCR) was used to detect BACH1 expression and other related metastatic genes following siRNA knockdown in colon cancer HT-29 cells. And the protein level assessed by Western blot. MTT assay was to measure the changed cell viability after BACH1 siRNA transfection. Scratch-wound motility assays measured capacity of tumor cell migration of HT-29 cells after BACH1 silencing. Results The inhibitory effect of BACH1 was performed by siRNA knockdown using highly metastatic HT-29 colon cell lines. Quantitative RT-PCR and Western blot analysis revealed that the expression levels of BACH1 mRNA and protein in HT29 cells were significantly suppressed after transfection. Conversely, the BACH1 expression increased migration. Also the CXCR4 and MMP1 expression levels decreased following BACH1 knockdown in HT-29 cells. Conclusion Our results indicated that BACH1 down-regulation in HT29 CRC cells had no effect on cell growth but did inhibit cell migration by decreasing metastasis-related genes expression. Collectively, these results suggest that BACH1 may function as an oncogenic driver in colon cancer and may represent as a potential target of gene therapy for CRC treatment. [ABSTRACT FROM AUTHOR]

BACH1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1) is a transcriptional factor and a member of cap ‘n’ collar (CNC) and basic region leucine zipper factor family. In contrast to other bZIP family members, BACH1 appeared as a comparatively specific transcription factor. It acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative. In regard to studies lately, although, BACH1 has been related to the regulation of oxidative stress and heme oxidation, it has never been linked to invasion and metastasis. Recent studies have showed that BACH1 is involved in bone metastasis of breast cancer by up-regulating vital metastatic genes like CXCR4 and MMP1. This newly discovered aspect of BACH1 gene provides new insight into cancer progression study and stands on its master regulator role in metastasis process, raising the possibility of considering it as a potential target for cancer therapy. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs), a class of regulatory endogenous short RNAs, are involved in various biological functions by targeting the mRNA of multiple protein-coding genes and influencing their related signaling pathways. In this investigation, we upregulated microRNA-143 (miR-143) expression levels in bladder cancer (BC) EJ138 cells by pCMV-miR-143 vectors. The efficacy of transfection was verified by Flow cytometry. The influence of miR-143 overexpression on BC cells migration, proliferation, and apoptosis was detected using wound-healing assay, MTT assay, and DAPI and Annexin V/PI staining, respectively. The results demonstrated that upregulation of miR-143 in BC EJ138 cells leads to inhibited proliferation and migration. Also, restoration of miR-143 was negatively associated with the expression levels of metastatic, apoptotic, invasion, and EMT-related genes, including C-Myc, CXCR4, MDM2, Vimentin, Snail-1, and MMP-9, along with increased E-Cadherin and TP53 expression. Therefore, miR-143 may be considered a potential therapeutic target for BC. [Display omitted] • Restoration of miR-143 significantly reduces cell proliferation and migration of bladder cancer cells (EJ138). • miR-143 involves different major signaling pathways involved in EMT, such as AKT , ERK , MAPK , and NF-κB. • The expression level of C-myc , MMP-9 , Snail-1 , CXCR4 , MDM2, and Vimentin downregulated by replacement of mir-143. • The expression level of E-cadherin and TP53 is upregulated by restoration of mir-143. [ABSTRACT FROM AUTHOR]