MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

Imani, Saber; Wei, Chunli; Cheng, Jingliang; Khan, Md. Asaduzzaman; Fu, Shangyi; Yang, Luquan; Tania, Mousumi; Zhang, Xianqin; Xiao, Xiuli; Zhang, Xianning; Fu, Junjiang

doi:10.18632/oncotarget.15214

Cited by 102 publications

(83 citation statements)

References 77 publications

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“…In addition to these chemopotentiating effect, TQ is recently found to synergize with miR-34a, a microRNA which targets various epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) including twist-related protein 1 (TWIST1), SLUG, and NOTCH1 (Imani et al, 2017). Overall, TQ was found to show almost all the favorable characteristics of an ideal adjuvant agents that can be used along with a wide variety of main course anticancer chemotherapeutic drugs.…”

Section: Chemo-potentiating Role Of Tqmentioning

confidence: 99%

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

et al. 2017

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Thymoquinone (TQ), the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological properties of TQ to rationalize its supplementary role in potentiating the efficacy of standard therapeutic modalities namely surgery, radiotherapy, chemotherapy, and immunotherapy. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical levels to delineate its implied utility as a novel complementary adjuvant therapy for cancer treatment.

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Section: Chemo-potentiating Role Of Tqmentioning

confidence: 99%

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

et al. 2017

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“…The overexpression of miR-21 and miR-155, and lost expression of miR-200 and let-7 are responsible for BC progression [15]. The microRNA-34a was authenticated to be a migration inhibitor by targeting EMT transcription factors in BC [16]. The cluster of mir-183/-96/-182 which is under the direct regulation of HSF2 and ZEB1 significantly overexpresses in BC subtypes as oncomiRs.…”

Section: Introductionmentioning

confidence: 99%

Unearthing Regulatory Axes of Breast Cancer circRNAs Networks to Find Novel Targets and Fathom Pivotal Mechanisms

Afzali

Salimi

2019

Preprint

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Circular RNAs (circRNAs) along other complementary regulatory elements in ceRNAs networks possess valuable characteristics for both diagnosis and treatment of several human cancers including breast cancer (BC). In this study, we combined several systems biology tools and approaches to identify influential BC circRNAs, RNA binding proteins (RBPs), miRNAs, and related mRNAs to study and decipher the BC triggering biological processes and pathways.Rooting from the identified total of 25 co-differentially expressed circRNAs (DECs) between triple negative (TN) and luminal A subtypes of BC from microarray analysis, five hub DECs (hsa_circ_0003227, hsa_circ_0001955, hsa_circ_0020080, hsa_circ_0001666, and hsa_circ_0065173) and top eleven RBPs (AGO1, AGO2, EIF4A3, FMRP, HuR (ELAVL1), IGF2BP1, IGF2BP2, IGF2BP3, EWSR1, FUS, and PTB) were explored to form the upper stream regulatory elements. All the hub circRNAs were regarded as super sponge having multiple miRNA response elements (MREs) for numerous miRNAs. Then four leading miRNAs (hsa-miR-149, hsa-miR-182, hsa-miR-383, and hsa-miR-873) accountable for BC progression were also introduced from merging several ceRNAs networks. The predicted 7-and 8-mer MREs matches between hub circRNAs and leading miRNAs ensured their enduring regulatory capability. The mined downstream mRNAs of the circRNAs-miRNAs network then were presented to STRING database to form the PPI network and deciphering the issue from another point of view. The BC interconnected enriched pathways and processes guarantee the merits of the ceRNAs networks' members as targetable therapeutic elements. This study suggested extensive panels of novel covering therapeutic targets that are in charge of BC progression in every aspect, hence their impressive role cannot be excluded and needs deeper empirical laboratory designs. Breast cancer (BC) is the most lethal cancer among women worldwide in 2017 [1]. To surpass the anti-cancer treatments' deficiencies, exploitation of all the novel high throughput data rooting from underlying microlayers of a disease is critical. Competing endogenous RNAs (ceRNAs) network which consists of various transcripts regulating each other at post-transcriptional level [2], is a complex and yet novel tracing means to investigate the breast cancer progression and metastasis. The interrelation between the transcripts that possess miRNA response elements (MREs), namely circular RNAs (circRNAs) and mRNAs is pivotal in the deciphering steps. The fundamental core of the ceRNA network is based on the ratio of affinity and competing for shared miRNAs MREs [3]. The circRNAs that were surmised to be non-coding, are now believed to be translated into proteins [4]. Apropos of being resistant to exonucleases and being more stable due to the lack of cap and poly A tales in their structure [5], possess myriad noteworthy functions in genes' expression regulations in cancer. They are divided into three subcategories regarding their source of emergence; exonic circRNA (ecRNA), exon-intron circRNA (ElciRNA)...

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“…miR‐34a and miR‐10b target/regulate some of stemness genes and EMT factors but with lower correlation to both pathways. The role of both miRNAs in BCSCs has been reported previously in several studies . The pathway analysis revealed that these genes were significantly related to the “CAMs,” “pathways in cancer,” “MAPK signalling pathway,” “Wnt signalling pathway,” “Hedgehog signalling pathway,” “Hippo signalling pathway,” “TGF‐β signalling pathway,” “Signalling pathways regulating pluripotency of stem cells,” “p53 signalling pathway,” “ABC transporters,” and “Cell cycle.” All these pathways have been demonstrated to be linked to various cellular activities including proliferation, migration, invasion, formation of multicellular spheroid, regulation of oestrogen receptor signalling, cancer progression, metastasis, self‐renewal in cancer and CSCs, maintenance of EMT and stemness, and breast cancer chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

“…The role of both miRNAs in BCSCs has been reported previously in several studies. [52][53][54] The pathway analysis revealed that these genes were significantly related to the "CAMs," "pathways in cancer,"…”

Section: Discussionmentioning

confidence: 99%

An integrated analysis to predict micro‐RNAs targeting both stemness and metastasis in breast cancer stem cells

Rahimi

Sharifi‐Zarchi

Firouzi

et al. 2019

J Cellular Molecular Medi

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Several evidences support the idea that a small population of tumour cells representing self‐renewal potential are involved in initiation, maintenance, metastasis, and outcomes of cancer therapy. Elucidation of microRNAs/genes regulatory networks activated in cancer stem cells (CSCs) is necessary for the identification of new targets for cancer therapy. The aim of the present study was to predict the miRNAs pattern, which can target both metastasis and self‐renewal pathways using integration of literature and data mining. For this purpose, mammospheres derived from MCF‐7, MDA‐MB231, and MDA‐MB468 were used as breast CSCs model. They had higher migration, invasion, and colony formation potential, with increasing in stemness‐ and EMT‐related genes expression. Our results determined that miR‐204, ‐200c, ‐34a, and ‐10b contemporarily could target both self‐renewal and EMT pathways. This core regulatory of miRNAs could increase the survival rate of breast invasive carcinoma via up‐regulation of OCT4, SOX2, KLF4, c‐MYC, NOTCH1, SNAI1, ZEB1, and CDH2 and down‐regulation of CDH1 . The majority of those target genes were involved in the regulation of pluripotency, MAPK, WNT, Hedgehog, p53, and transforming growth factor β pathways. Hence, this study provides novel insights for targeting core regulatory of miRNAs in breast CSCs to target both self‐renewal and metastasis potential and eradication of breast cancer.

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MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

Cited by 102 publications

References 77 publications

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

Unearthing Regulatory Axes of Breast Cancer circRNAs Networks to Find Novel Targets and Fathom Pivotal Mechanisms

An integrated analysis to predict micro‐RNAs targeting both stemness and metastasis in breast cancer stem cells

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