<i>Retracted</i>: miR‐200c, a tumor suppressor that modulate the expression of cancer stem cells markers and epithelial‐mesenchymal transition in colorectal cancer

Dermani, Fateme Karimi; Amini, Razieh; Saidijam, Massoud; Najafi, Rezvan

doi:10.1002/jcb.26880

Cited by 20 publications

(9 citation statements)

References 44 publications

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“…In addition, PLEKHA7 re-expression results in the increased levels of miRNAs that we have previously identified to be regulated by PLEKHA7 in Caco2 cells, such as miR-30b, miR-200c, and miR-203a ( Figure 5I) [10,25]. These miRNAs are well-established tumor suppressors and are downregulated in many cancers, including colorectal tumors, as well as in colon cancer cell lines, such as those included in our study [38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Together, these results are in agreement with our previous findings [10,25] and further support a tumor suppressing role for PLEKHA7 in the colonic epithelium, through recruitment and regulation of the RNAi machinery.…”

Section: Plekha7 Re-expression In Hct116 Cells Restores Junctional Lomentioning

confidence: 99%

Predominant Distribution of the RNAi Machinery at Apical Adherens Junctions in Colonic Epithelia Is Disrupted in Cancer

Nair-Menon

Daulagala

Connor

et al. 2020

IJMS

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The RNA interference (RNAi) machinery is an essential component of the cell, regulating miRNA biogenesis and function. RNAi complexes were thought to localize either in the nucleus, such as the microprocessor, or in the cytoplasm, such as the RNA-induced silencing complex (RISC). We recently revealed that the core microprocessor components DROSHA and DGCR8, as well as the main components of RISC, including Ago2, also associate with the apical adherens junctions of well-differentiated cultured epithelial cells. Here, we demonstrate that the localization of the core RNAi components is specific and predominant at apical areas of cell-cell contact of human normal colon epithelial tissues and normal primary colon epithelial cells. Importantly, the apical junctional localization of RNAi proteins is disrupted or lost in human colon tumors and in poorly differentiated colon cancer cell lines, correlating with the dysregulation of the adherens junction component PLEKHA7. We show that the restoration of PLEKHA7 expression at adherens junctions of aggressively tumorigenic colon cancer cells restores the junctional localization of RNAi components and suppresses cancer cell growth in vitro and in vivo. In summary, this work identifies the apical junctional localization of the RNAi machinery as a key feature of the differentiated colonic epithelium, with a putative tumor suppressing function.

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Section: Plekha7 Re-expression In Hct116 Cells Restores Junctional Lomentioning

confidence: 99%

Predominant Distribution of the RNAi Machinery at Apical Adherens Junctions in Colonic Epithelia Is Disrupted in Cancer

Nair-Menon

Daulagala

Connor

et al. 2020

IJMS

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“…As EZH2 determines HCC progression and metastasis, we next sought to investigate its role in miR-200c mediated tumorigenesis. It has been reported that miR-200c was a tumor suppressor microRNA in many cancers, such as colorectal cancer, renal cell carcinoma 27,28 . However, the in vivo role of miR-200c in HCC tumor cell growth has yet to be elucidated.…”

Section: Silencing Mir-200c Rescues the Sphere Formation And Migratiomentioning

confidence: 99%

EZH2 facilitates BMI1-dependent hepatocarcinogenesis through epigenetically silencing microRNA-200c

Lin

Deng

et al. 2020

Oncogenesis

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EZH2, a histone methyltransferase, has been shown to involve in cancer development and progression via epigenetic regulation of tumor suppressor microRNAs, whereas BMI1, a driver of hepatocellular carcinoma (HCC), is a downstream target of these microRNAs. However, it remains unclear whether EZH2 can epigenetically regulate microRNA expression to modulate BMI1-dependent hepatocarcinogenesis. Here, we established that high EZH2 expression correlated with enhanced tumor size, elevated metastasis, increased relapse, and poor prognosis in HCC patients. Further clinical studies revealed that EZH2 overexpression was positively correlated to its gene copy number gain/amplification in HCC. Mechanistically, EZH2 epigenetically suppressed miR-200c expression both in vitro and in vivo, and more importantly, miR-200c post-transcriptionally regulated BMI1 expression by binding to the 3′-UTR region of its mRNA. Furthermore, miR-200c overexpression inhibits the growth of HCC cells in vivo. Silencing miR-200c rescued the tumorigenicity of EZH2-depleted HCC cells, whereas knocking down BMI1 reduced the promoting effect of miR-200c depletion on HCC cell migration. Finally, combination treatment of EZH2 and BMI1 inhibitors further inhibited the viability of HCC cells compared with the cells treated with EZH2 or BMI1 inhibitor alone. Our findings demonstrated that alteration of EZH2 gene copy number status induced BMI1-mediated hepatocarcinogenesis via epigenetically silencing miR-200c, providing novel therapeutic targets for HCC treatment.

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“…Hence, miRNAs identification in cancer tissues and body fluids potentially have great clinical utility in early diagnosis and prognosis. However, the translation of miRNA-based knowledge to clinical practice in the treatment of CRC has not yet been achieved, and the impact of miRNAs on stem cell and colorectal CSC biology has emerged only recently [23][24][25][26][27][28][29]. Moreover, many reports in the scientific literature have been either in vitro or patientbased studies, and there are few studies aimed to identify colorectal CSC-associated miRNAs and their usefulness as tissue and/or serum biomarker in CRC patients.…”

Section: Introductionmentioning

confidence: 99%

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

et al. 2020

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Copyright: Farace et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACTColorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH + and CD44 + /CD326 + colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients' samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted. www.oncotarget.com

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Retracted: miR‐200c, a tumor suppressor that modulate the expression of cancer stem cells markers and epithelial‐mesenchymal transition in colorectal cancer

Cited by 20 publications

References 44 publications

Predominant Distribution of the RNAi Machinery at Apical Adherens Junctions in Colonic Epithelia Is Disrupted in Cancer

Predominant Distribution of the RNAi Machinery at Apical Adherens Junctions in Colonic Epithelia Is Disrupted in Cancer

EZH2 facilitates BMI1-dependent hepatocarcinogenesis through epigenetically silencing microRNA-200c

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

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