miR-6734 Up-Regulates p21 Gene Expression and Induces Cell Cycle Arrest and Apoptosis in Colon Cancer Cells

Kang, Moo Rim; Park, Ki Hwan; Yang, Jeong-Ook; Lee, Chang Woo; Oh, Soo Jin; Yun, Jieun; Lee, Myeong Youl; Han, Sang‐Bae; Kang, Jong Soon

doi:10.1371/journal.pone.0160961

Cited by 39 publications

(28 citation statements)

References 26 publications

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“…Similar result has been reported about miR-6734 in the colon cancer cell HCT116 [39]. In this study, miRNA microarray identified 17 miRNAs, including miR-663a, as upregulated miRNAs in HCT116.…”

Section: Discussionsupporting

confidence: 88%

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

et al. 2017

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BackgroundAntimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown.MethodsmiRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs. Establishment of miR-663a over-expressing HCT116 cells was carried out for the evaluation of growth both in vitro and in vivo. To identify the molecular mechanisms, we used western blotting analysis.ResultsmiR-663a is upregulated by administration of the human cathelicidin AMP, LL-37, and its analogue peptide, FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in vitro and in vivo. We also provide evidence supporting the view that these effects are attributed to suppression of the expression of the chemokine receptor CXCR4, resulting in the abrogation of phosphorylation of Akt and cell cycle arrest in G2/M via p21 activation.ConclusionsThis study contributes to the understanding of the AMPs’ mediated anti-cancer mechanisms in colon cancer cells and highlights the possibility of using AMPs and miRNAs towards developing future strategies for cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3003-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 88%

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

et al. 2017

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“…Ensuing in vivo studies utilizing a xenograft model demonstrated that nanoparticle-mediated delivery of miR-124 could reduce tumor growth and sensitize cells to etoposide to increase apoptosis [ 102 ]. Similarly, miR-6734 was found to inhibit the growth of colon cancer cells by up-regulating p21 gene expression and subsequent induction of cell cycle arrest and apoptosis [ 103 ]. The binding site of miR-877-3p was also found on the promoter site of tumor suppressor gene p16 .…”

Section: Microrna Nuclear Functions In Cancermentioning

confidence: 99%

Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer

et al. 2018

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MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain approximately 22 nucleotides. They serve as key regulators in various biological processes and their dysregulation is implicated in many diseases including cancer and autoimmune disorders. It has been well established that the maturation of miRNAs occurs in the cytoplasm and miRNAs exert post-transcriptional gene silencing (PTGS) via RNA-induced silencing complex (RISC) pathway in the cytoplasm. However, numerous studies reaffirm the existence of mature miRNA in the nucleus, and nucleus-cytoplasm transport mechanism has also been illustrated. Moreover, active regulatory functions of nuclear miRNAs were found including PTGS, transcriptional gene silencing (TGS), and transcriptional gene activation (TGA), in which miRNAs bind nascent RNA transcripts, gene promoter regions or enhancer regions and exert further effects via epigenetic pathways. Based on existing interaction rules, some miRNA binding sites prediction software tools are developed, which are evaluated in this article. In addition, we attempt to explore and review the nuclear functions of miRNA in immunity, tumorigenesis and invasiveness of tumor. As a non-canonical aspect of miRNA action, nuclear miRNAs supplement miRNA regulatory networks and could be applied in miRNA based therapies.

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“…[16][17][18] However, accumulating evidence suggested that miRNAs hold the ability to activate gene expression by targeting promoters. 2,[19][20][21] Place et al reported that miR-373 can induce E-cadherin expression with complementary promoter sequence. Recent studies have also reported that miR-6734 and miR-3619 had the capacity to activate p21 gene expression in breast cancer (BC) and colon cancer, respectively.…”

Section: Introductionmentioning

confidence: 99%

Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells

Liu

et al. 2017

Tumour Biol.

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The mechanism of dsRNA-induced gene activation (RNAa) is being gradually unveiled. The plentiful evidence that it existed in mammalian species other than human demonstrated that dsRNA-mediated RNAa is a conservative phenomenon. Simultaneously, accumulating evidence suggested that microRNAs could activate gene expression by targeting promoter. Nevertheless, it is ambiguous whether microRNA-induced gene activation in different human cells is a common phenomenon. The study we performed verified that miR-1236-3p (miR-1236) and miR-370-5p can activate p21 expression in bladder cancer (BCa) T24, EJ cells, and non-small-cell lung carcinoma A549 cells, while in hepatocellular HepG2 cells both microRNAs cannot effectively induce the expression of P21 (p21). In pancreatic cancer PANC-1 cells, only miR-370-5p had the potent abilities to induce p21 expression rather than miR-1236-3p. Unlike microRNA-mediated RNA activation, we can observe that dsP21-322 significantly activated p21 in above cells. Besides, we demonstrated that miR-1236 and miR-370 inhibited cyclin D1-CDK4/CDK6 pathway while upregulated E-cadherin expression by upregulation of p21. Overexpression of these two microRNAs in A549 induced cell-cycle arrest and cell senescence, delayed cell proliferation and colony formation, and inhibited migration and invasion. In conclusion, microRNA-mediated RNAa depends on the cell context, and miR-1236 and miR-370 can inhibit non-small-cell lung carcinoma cell growth by upregulating p21 expression in vitro.

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miR-6734 Up-Regulates p21 Gene Expression and Induces Cell Cycle Arrest and Apoptosis in Colon Cancer Cells

Cited by 39 publications

References 26 publications

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer

Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells

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