MicroRNA <i>MIR21</i> (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival

Mima, Kosuke; Nishihara, Reiko; Yang, Juhong; Dou, Ruoxu; Masugi, Yohei; Shi, Yan; Silva, Annacarolina da; Cao, Yin; Song, Mingyang; Nowak, Jonathan A.; Gu, Mancang; Li, Wanwan; Morikawa, Teppei; Zhang, Xuehong; Wu, Kana; Baba, Hideo; Giovannucci, Edward; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji

doi:10.1158/1078-0432.ccr-15-2173

Cited by 55 publications

(43 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This structural similarity between miR-21 and PTEN is a powerful mechanism explanation of miR-21's downregulatory effect on PTEN protein expression. A negative association has previously been demonstrated between PTEN and Akt activation (24). However, some limitations and unsolved problems remain in the present study, such as the detailed mechanism of metformin's inhibitory effect on miR-21 and whether other signaling pathways are also involved in this effect.…”

Section: Discussionmentioning

confidence: 73%

Metformin inhibits HaCaT cell viability via the miR-21/PTEN/Akt signaling pathway

Deng

2017

Mol Med Report

View full text Add to dashboard Cite

Substantial preclinical evidence has indicated out a direct anti‑proliferation effect of metformin on various solid tumors; however, further and more detailed exploration into its molecular mechanism remains to be performed. The present study aimed to investigate the effect of metformin on cell viability and its underlying mechanism, in the cultured human skin keratinocyte cell line, HaCaT. In addition, it aimed to clarify the role of the microRNA-21(miR-21)/phosphatase and tensin homolog (PTEN)/AKT serine/threonine kinase 1 (Akt) signaling pathway, which has been hypothesized to be involved in the molecular mechanism of this drug. Cell Counting Kit‑8 assays were used to assess the impact of metformin on cell viability; reverse transcription‑quantitative polymerase chain reaction was used to quantify the expression of miR‑21; western blotting was used to monitor the expression level of PTEN and Akt proteins. In addition, miR‑21 expression levels were artificially manipulated in HaCaT cells using a miR‑21 inhibitor in order to observe the subsequent expression changes of miR‑21 targets and alterations in cell viability. The results indicated that metformin suppressed HaCaT cell growth in a dose‑ and time‑dependent manner (P<0.05). Metformin treatment downregulated miR‑21 expression (t=‑8.903, P<0.05). Following transfection with the miR‑21 inhibitor, HaCaT cell growth was significantly slower than in the control groups (P<0.05). In addition, reduced miR‑21 levels results in significantly increased PTEN protein expression levels and reduced Akt protein expression levels compared with control (P<0.05). Metformin was, therefore, concluded to inhibit HaCaT cell growth in a time‑and dose‑dependent manner, and the miR‑21/PTEN/Akt signaling pathway may serve a crucial role in the molecular mechanism of metformin's effect on HaCaT cells. Therefore the present study presents an advanced insight into the potential inhibitory effect of metformin on tumor cells.

show abstract

Section: Discussionmentioning

confidence: 73%

Metformin inhibits HaCaT cell viability via the miR-21/PTEN/Akt signaling pathway

Deng

2017

Mol Med Report

View full text Add to dashboard Cite

show abstract

“…We have previously reported that human T FH cells are one of the only human lymphocyte subsets expressing baseline CD137 in healthy conditions (14). Modulation of CD137-dependent epigenetic changes in the TCF7 locus, which encodes the TCF1 transcription factor, is of considerable interest, because this pathway orchestrates the stemness of T cells (46), as well as their exhausted phenotype (35,37,46). Along this line of reasoning, TCF1 reduction could mitigate undesired functional phenotypes of CD8 þ T cells, thereby potentially enhancing tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

CD137 (4-1BB) Costimulation Modifies DNA Methylation in CD8+ T Cell–Relevant Genes

Aznar

Labiano

Díaz‐Lagares

et al. 2018

Cancer Immunology Research

View full text Add to dashboard Cite

CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA methylation arrays were carried out on human peripheral blood CD8 T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy. Several genes showed consistent methylation patterns in response to CD137 costimulation, which were confirmed by pyrosequencing in a series of healthy donors. , and were among the immune-related genes regulated by differential DNA methylation, leading to changes in mRNA and protein expression. These genes are also differentially methylated in naïve versus antigen-experienced CD8 T cells. The transcription factor TCF1 and the microRNA miR-21 were regulated by DNA methylation upon CD137 costimulation. Such gene-expression regulatory factors can, in turn, broaden the effects of DNA methylation by controlling expression of their target genes. Overall, chromatin remodeling is postulated to leave CD137-costimulated T lymphocytes poised to differentially respond upon subsequent antigen recognition. Accordingly, CD137 connects costimulation during priming to genome-wide DNA methylation and chromatin reprogramming. .

show abstract

“…For this reason, our study aimed to expand the first findings in order to gain a better understanding of the tumor biology of RCC. Similarly to miR-1, miR-21 was also detected in various malignant tissues, such as prostate and lung cancer and their metastases, pancreatic cancer and colorectal cancer (17)(18)(19)(20)(21). However, in contrast to miR-1, miR-21 appears to be an oncomir.…”

mentioning

confidence: 99%

MicroRNA-1 and MicroRNA-21 Individually Regulate Cellular Growth of Non-malignant and Malignant Renal Cells

Ahrend

Kaul

Ziegler

et al. 2017

View full text Add to dashboard Cite

Abstract. Background/Aim: Due to its poor prognosis, it is increasingly necessary to understand the biology of renal cell cancer (RCC). Therefore, we investigated the role of microRNAs miR-1 and miR-21 in the growth of RCC cells compared to that of non-malignant renal cells. Materials and Methods: Four malignant cell lines RCC4, A498) Tumorigenesis gives cells an advantage in survival by an increase of proliferation, angiogenesis, immunomodulation and immortality (1-4). Due to its delayed diagnosis until advanced stages, renal cell cancer (RCC) is known as the deadliest neoplasm of the urinary tract (1, 5). Thus, it is more necessary than ever to understand its tumor biology and explore new targets for further therapeutic approaches and prognostic options (6). Former studies suggested that among others, a misguided microRNA expression pattern may be involved in tumor initiation and progression in RCC (7,8). Among such mechanisms, small regulatory RNAs, so-called microRNAs (miRs), can operate as controllers of different proccesses in tumorigenesis, such as cell migration and differentiation, as well as metastasis and apoptosis (9-11). miR-1 and miR-21 are two of numerous representatives of microRNAs. miR-1, initially found in cardiac muscle cells (12), but also found in various tissues (13-15), was strongly suspected of acting as a tumor suppressor due to its antioncogenic properties (16) in prostate, breast and colorectal cancer (13-15); interestingly, the type of tissue in fact determines the biological behavior of miR-1 (9). Sadly, the current data situation for the expression of miR-1 in RCC leaves much to be desired. For this reason, our study aimed to expand the first findings in order to gain a better understanding of the tumor biology of RCC. Similarly to miR-1, miR-21 was also detected in various malignant tissues, such as prostate and lung cancer and their metastases, pancreatic cancer and colorectal cancer (17-21). However, in contrast to miR-1, miR-21 appears to be an oncomir. There are preliminary investigations, showing miR-21 to appear as an oncomir in the case of RCC (22, 23).The fact that cancer cells have a further survival advantage by extending their chromosomal ends by means of endogenic telomerase, not only raises a problem, but also provides a therapeutic approach in cancer therapy (4).In order to gain deeper insight into these issues, as far as we are aware, we are the first to investigate one non-malignant 625 This article is freely accessible online. *These Authors contributed equally to this study. Materials and MethodsCell culture. Human RCC cell lines Caki-1, 786-O, A498 (all Cell Lines Service, Eppelheim, Germany), and RCC4 (Sigma-Aldrich, München, Germany) and the non-malignant renal cell line RC-124 (Cell Lines Service) were applied in this study. Caki-1 and A498 cells were propagated in minimum essential medium (MEM) supplemented with 79.6 mg/l non-essential amino acids, 2 mM L-glutamine, 1 mM sodium pyruvate, 1% penicillline/streptomycin (P/S), and 10% fetal bovine serum (FBS...

show abstract

MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival

Cited by 55 publications

References 53 publications

Metformin inhibits HaCaT cell viability via the miR-21/PTEN/Akt signaling pathway

Metformin inhibits HaCaT cell viability via the miR-21/PTEN/Akt signaling pathway

CD137 (4-1BB) Costimulation Modifies DNA Methylation in CD8+ T Cell–Relevant Genes

MicroRNA-1 and MicroRNA-21 Individually Regulate Cellular Growth of Non-malignant and Malignant Renal Cells

Contact Info

Product

Resources

About