Targeting microRNAs in epithelial-to-mesenchymal transition-induced cancer stem cells: therapeutic approaches in cancer

Garg, Minal

doi:10.1517/14728222.2014.975794

Cited by 59 publications

(46 citation statements)

References 76 publications

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“…19 Given the fact that EMT participates in the tumorigenesis and provide important indications for cancer progression, we may get inspirations on the therapeutic role of circRNA by targeting microRNA involved in EMT. 20,21 Meanwhile, intronic circRNAs are produced when lariats that escape the debranching enzymes are processed by exonucleases. The formation of circular intronic RNAs (ciRNAs) can be recapitulated using expression vectors.…”

Section: Biogenesis and Functionmentioning

confidence: 99%

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

2016

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Circular RNAs (circRNAs) are long, non-coding RNAs that result from the non-canonical splicing of linear premRNAs. However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the "microRNA sponge" function of circRNA is discovered. Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively. In this review, we illustrate the specific role of circRNAs in a wide variety of cancers and in regulating the biological behavior of cancers via miR-7 or miR-138 regulation. Furthermore, circRNA, together with its gene silencing ability, also shows its potential in RNA interference (RNAi) therapy by binding to target RNAs, which provides a novel perspective in cancer treatment. Thus, this review concerns the biogenesis, biological function, oncogenesis, progression and possible therapies for cancer involving circRNAs.

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Section: Biogenesis and Functionmentioning

confidence: 99%

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

2016

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“…Uncovering that miRNA is linked to prognosis, progression, local recurrence (Sato-Kuwabara et al, 2015), and contributes to EMT (Garg, 2015), fostered progress in oncology. In concern about CD44, miR-34a overexpression inhibits metastasis by regulating CD44 and miR-340 suppresses invasion and metastasis by regulating CD44-associated c-Met and metalloproteinases (MMP) 2 and 9 (Liu et al, 2011; Wu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

Wang

Zhao

Hackert

et al. 2018

Front. Cell Dev. Biol.

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Metastasis is the leading cause of cancer death, tumor progression proceeding through emigration from the primary tumor, gaining access to the circulation, leaving the circulation, settling in distant organs and growing in the foreign environment. The capacity of a tumor to metastasize relies on a small subpopulation of cells in the primary tumor, so called cancer-initiating cells (CIC). CIC are characterized by sets of markers, mostly membrane anchored adhesion molecules, CD44v6 being the most frequently recovered marker. Knockdown and knockout models accompanied by loss of tumor progression despite unaltered primary tumor growth unraveled that these markers are indispensable for CIC. The unexpected contribution of marker molecules to CIC-related activities prompted research on underlying molecular mechanisms. This review outlines the contribution of CD44, particularly CD44v6 to CIC activities. A first focus is given to the impact of CD44/CD44v6 to inherent CIC features, including the crosstalk with the niche, apoptosis-resistance, and epithelial mesenchymal transition. Following the steps of the metastatic cascade, we report on supporting activities of CD44/CD44v6 in migration and invasion. These CD44/CD44v6 activities rely on the association with membrane-integrated and cytosolic signaling molecules and proteases and transcriptional regulation. They are not restricted to, but most pronounced in CIC and are tightly regulated by feedback loops. Finally, we discuss on the engagement of CD44/CD44v6 in exosome biogenesis, loading and delivery. exosomes being the main acteurs in the long-distance crosstalk of CIC with the host. In brief, by supporting the communication with the niche and promoting apoptosis resistance CD44/CD44v6 plays an important role in CIC maintenance. The multifaceted interplay between CD44/CD44v6, signal transducing molecules and proteases facilitates the metastasizing tumor cell journey through the body. By its engagement in exosome biogenesis CD44/CD44v6 contributes to disseminated tumor cell settlement and growth in distant organs. Thus, CD44/CD44v6 likely is the most central CIC biomarker.

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“…Hence, targeting cancer cells with an EGFR inhibitor (anti-EGFR antibody, cetuximab) has been shown to increase the expression of CDH1 and confer cancer cells with epithelial phenotypic property [24] . Implications of miRNAs (a class of small non-coding RNA molecules of 21-23 nucleotides in length) in the maintenance of epithelial plasticity, cancer stemness and mediating drug sensitivities make it a potential therapeutic system towards eradication of tumor recurrence and metastasis [25,26] . Forced expression of miR-200 family (miR200a, miR-200b, miR-200c, miR-141, and miR-429) has been associated with induction of MET in mesenchymal bladder cancer cell lines, which thereby restored EGFR inhibitor sensitivity to attenuate tumor aggressiveness in bladder cancer [25] .…”

Section: Therapeutic Implications and Challengesmentioning

confidence: 99%

“…Implications of miRNAs (a class of small non-coding RNA molecules of 21-23 nucleotides in length) in the maintenance of epithelial plasticity, cancer stemness and mediating drug sensitivities make it a potential therapeutic system towards eradication of tumor recurrence and metastasis [25,26] . Forced expression of miR-200 family (miR200a, miR-200b, miR-200c, miR-141, and miR-429) has been associated with induction of MET in mesenchymal bladder cancer cell lines, which thereby restored EGFR inhibitor sensitivity to attenuate tumor aggressiveness in bladder cancer [25] . Re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer by targeting Zeb1, a crucial regulator of EMT, inhibiting cell proliferation and migration and inducing apoptosis [27] .…”

Section: Therapeutic Implications and Challengesmentioning

confidence: 99%

Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

Garg¹

2016

WJSC

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Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells. Core tip: A subset of bladder cancer cells, known as urothelial cancer stem cells, have abilities to self-renew, generate tumor heterogeneity via differentiation, and are actually responsible for tumor relapse and metastasis formation. Delineating the mechanistic complexity between epithelial plasticity and cancer stemness in malignant transformation of urothelial carcinoma provides the basis for designing rational therapies. Differentiation and elimination therapies targeting the potential biomarkers could prove to be clinically beneficial by suppressing the cancer stemness and inhibiting epithelial-to-mesenchymal transition phenotype and would provide novel opportunities for targeted therapeutic approaches in the clinical management of patients.

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Targeting microRNAs in epithelial-to-mesenchymal transition-induced cancer stem cells: therapeutic approaches in cancer

Cited by 59 publications

References 76 publications

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

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