Let-7a inhibits tumor cell growth and metastasis by directly targeting RTKN in human colon cancer

Li, Bin; Chen, Peng; Chang, Yanxiang; Qi, Junyuan; Fu, Hui; Guo, Haipeng

doi:10.1016/j.bbrc.2016.08.018

Cited by 24 publications

(18 citation statements)

References 36 publications

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“…et al, 2017 ). On the contrary, augmented serum levels of let-7a and miR-150 were inconsistent with their documented downregulation and tumor suppressive property in CRC (Ma Y. et al, 2012 ; Li et al, 2016 ). Recently, another study on serum exosomes from CRC patients reported the upregulation of miR-486-5p and miR-3180-5p, and the downregulation of miR-548c-5p, miR-638, miR-5787, miR-6869-5p, miR-8075 (Yan et al, 2017 ).…”

Section: Exosomal Mirnas Appear To Be Promising Biomarkers In Cancer mentioning

confidence: 96%

“…This approach could be considered misleading: a part of altered circulating miRNAs in body fluids of cancer patients has a relative expression that is largely different from the one in the corresponding diseased tissues. The tumor suppressor miRNA let-7a inhibits tumor cell growth and metastasis in CRC and its levels are significantly decreased in CRC tissues and cell lines (Li et al, 2016 ); nevertheless, its exosomal levels in serum of CRC patients are increased (Ogata-Kawata et al, 2014 ). This apparent incongruity might be the result of a strategy adopted by the cancer to remove from cells miRNAs that are disadvantageous for viability and dissemination of CRC.…”

Section: Exosomal Mirnas Appear To Be Promising Biomarkers In Cancer mentioning

confidence: 99%

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Asymmetric RNA Distribution among Cells and Their Secreted Exosomes: Biomedical Meaning and Considerations on Diagnostic Applications

Ragusa

Barbagallo

Cirnigliaro

et al. 2017

Front. Mol. Biosci.

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Over the past few years, exosomes and their RNA cargo have been extensively studied because of the fascinating biological roles they play in cell-to-cell communication, including the signal exchange among cancer, stromal, and immune cells, leading to modifications of tumor microenvironment. RNAs, especially miRNAs, stored within exosomes, seem to be among the main determinants of such signaling: their sorting into exosomes appears to be cell-specific and related to cellular physiopathology. Accordingly, the identification of exosomal miRNAs in body fluids from pathological patients has become one of the most promising activity in the field of biomarker discovery. Several analyses on the qualitative and quantitative distribution of RNAs between cells and their secreted exosomes have given rise to questions on whether and how accurately exosomal RNAs would represent the transcriptomic snapshot of the physiological and pathological status of secreting cells. Although the exact molecular mechanisms of sorting remain quite elusive, many papers have reported an evident asymmetric quantitative distribution of RNAs between source cells and their exosomes. This phenomenon could depend both on passive and active sorting mechanisms related to: (a) RNA turnover; (b) maintaining the cytoplasmic miRNA:target equilibrium; (c) removal of RNAs not critical or even detrimental for normal or diseased cells. These observations represent very critical issues in the exploitation of exosomal miRNAs as cancer biomarkers. In this review, we will discuss how much the exosomal and corresponding donor cell transcriptomes match each other, to better understand the actual reliability of exosomal RNA molecules as pathological biomarkers reflecting a diseased status of the cells.

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Section: Exosomal Mirnas Appear To Be Promising Biomarkers In Cancer mentioning

confidence: 96%

Section: Exosomal Mirnas Appear To Be Promising Biomarkers In Cancer mentioning

confidence: 99%

Asymmetric RNA Distribution among Cells and Their Secreted Exosomes: Biomedical Meaning and Considerations on Diagnostic Applications

Ragusa

Barbagallo

Cirnigliaro

et al. 2017

Front. Mol. Biosci.

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“…Meanwhile, it had report that CXCR4 was inversely correlate with let-7a in acute myeloid leukemia [12]. It has been recognized that let-7a play suppressive role in tumorigenesis and chemosensitivity of cancer cells [19, 20, 28]. However, the role of CXCR4/let-7a in tumorigenesis and drug resistance of PCC remains not well-studied.…”

Section: Discussionmentioning

confidence: 99%

CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2

Xiao

Wang

2017

Cell Physiol Biochem

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Background/Aims: Pancreatic cancer cells (PCC) is one of the most risky cancers and gemcitabine (GEM) is the standard first-line drug for treating PCC. The PCC will develop drug resistance to GEM after a period of treatment. However, the detailed molecular mechanism of pathogenesis and drug resistance remains unresolved. Methods: we employed qRT-PCR and western blot to examine the expression level of CXCR4, let-7a and HMGA2. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness. The expression level of epithelial marker E-cadherin and mesenthymal marker N-cadherin was detected by western blot. The apoptosis was determined using annexin V-FITC/PI apoptosis detection kit by flow cytometry. Results: we first proved that CXCR4 negatively regulated let-7a in PCC. Next, let-7a was confirmed to play crucial role in tumorigenesis, metastasis and drug resistance of pancreatic cancer cells Bxpc-3 and Panc-1 in vitro and in vivo. Finally, we identified HMGA2 as important downsteam target of let-7a in PCC and overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of GEM inhibited by let-7a. Conlusion: Taken together, we show an important signaling pathway involved in pathogenesis and drug resistance of PCC, thereby providing deeper insight into molecular mechanism by which CXCR4/let-7a regulates tumorigenesis and drug resistance of PCC. These findings will help us develop new strategies for diagnosis and treatment of PCC.

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“…let‐7a has been mostly described in humans as a tumour suppressor by targeting cancer‐promoting genes in colon [36], prostate [37] and breast cancer [38]. In fibroblasts, downregulation of let‐7a has been found to promote type I collagen expression, while its overexpression reduced fibrosis [20].…”

Section: Discussionmentioning

confidence: 99%

Deregulation of miR‐27a may contribute to canine fibroblast activation after coculture with a mast cell tumour cell line

et al. 2020

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The tumour microenvironment comprises a diverse range of cells, including fibroblasts, immune cells and endothelial cells, along with extracellular matrix. In particular, fibroblasts are of significant interest as these cells are reprogrammed during tumorigenesis to become cancer‐associated fibroblasts (CAFs), which in turn support cancer cell growth. MicroRNAs (miRNAs) have been shown to be involved in this intercellular crosstalk in humans. To assess whether miRNAs are also involved in the activation of fibroblasts in dogs, we cocultured primary canine skin fibroblasts with the canine mast cell tumour cell line C2 directly or with C2‐derived exosomes, and measured differential abundance of selected miRNAs. Expression of the CAF markers alpha‐smooth muscle actin (ACTA2) and stanniocalcin 1 confirmed the activation of our fibroblasts after coculture. We show that fibroblasts displayed significant downregulation of miR‐27a and let‐7 family members. These changes correlated with significant upregulation of predicted target mRNAs. Furthermore, RNA interference knockdown of miR‐27a revealed that cyclin G1 (CCNG1) exhibited negative correlation at the mRNA and protein level, suggesting that CCNG1 is a target of miR‐27a in canine fibroblasts and involved in their activation. Importantly, miR‐27a knockdown itself resulted in fibroblast activation, as demonstrated by the formation of ACTA2 filaments. In addition, interleukin‐6 (IL‐6) was strongly induced in our fibroblasts when cocultured, indicating potential reciprocal signalling. Taken together, our findings are consistent with canine fibroblasts being reprogrammed into CAFs to further support cancer development and that downregulation of miR‐27a may play an important role in the tumour–microenvironment crosstalk.

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Let-7a inhibits tumor cell growth and metastasis by directly targeting RTKN in human colon cancer

Cited by 24 publications

References 36 publications

Asymmetric RNA Distribution among Cells and Their Secreted Exosomes: Biomedical Meaning and Considerations on Diagnostic Applications

Asymmetric RNA Distribution among Cells and Their Secreted Exosomes: Biomedical Meaning and Considerations on Diagnostic Applications

CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2

Deregulation of miR‐27a may contribute to canine fibroblast activation after coculture with a mast cell tumour cell line

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