• Title/Summary/Keyword: Tumor suppression

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A Novel Type of Non-coding RNA, nc886, Implicated in Tumor Sensing and Suppression

  • Lee, Yong Sun
    • Genomics & Informatics
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    • v.13 no.2
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    • pp.26-30
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    • 2015
  • nc886 (=vtRNA2-1, pre-miR-886, or CBL3) is a newly identified non-coding RNA (ncRNA) that represses the activity of protein kinase R (PKR). nc886 is transcribed by RNA polymerase III (Pol III) and is intriguingly the first case of a Pol III gene whose expression is silenced by CpG DNA hypermethylation in several types of cancer. PKR is a sensor protein that recognizes evading viruses and induces apoptosis to eliminate infected cells. Like viral infection, nc886 silencing activates PKR and induces apoptosis. Thus, the significance of the nc886:PKR pathway in cancer is to sense and eliminate pre-malignant cells, which is analogous to PKR's role in cellular innate immunity. Beyond this tumor sensing role, nc886 plays a putative tumor suppressor role as supported by experimental evidence. Collectively, nc886 provides a novel example how epigenetic silencing of a ncRNA contributes to tumorigenesis by controlling the activity of its protein ligand.

Suppression of colon cancer by administration of Canavalia gladiata D.C. and Arctium lappa L., Redix extracts in tumor-bearing mice model (종양이식 생쥐모델에서 도두(刀豆), 우방근(牛蒡根) 추출물의 대장암 억제 효과)

  • Jang, Ji-Hye;Ji, Kon-Young;Choi, Hyung-Seok;Yang, Won-Kyung;Kim, Han-Young;Kim, Kun-hoae;Kang, Hyung-Sik;Lee, Young-Cheol;Kim, Seung-Hyung
    • The Korea Journal of Herbology
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    • v.32 no.5
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    • pp.27-38
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    • 2017
  • Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

Study on Anti-tumor Activities of Both Hagocho and Byulap combined with Sambonggangyongbaneo-tang (삼봉강룡반어탕(三蓬薑龍半魚湯) 가(加) 하고초(夏枯草)와 加(가) 별갑(鱉甲)의 항암효과에 대한 비교연구)

  • Park, Jung-Sup;Jung, Seung-Min;Yim, Young-Nam;Ko, Ho-Yeun;Han, Ji-Wan;Kim, Dong-Woo
    • The Journal of Internal Korean Medicine
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    • v.25 no.4
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    • pp.242-251
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    • 2004
  • In this piece of research, Prunellae spica is added to Sambonggangyongbaneotang for one group and Trionycis carapax is added to Sambonggangyongbaneotang for the other group. With these two different prescriptions, the degrees of tumor suppression are compared to develop a better prescription. SKH = Sambonggangyongbaneo-tang + Prunellae Spica SKB = Sambonggangyongbaneo-tang + Trionycis Carapax The results were as follows: 1. SKH and SKB demonstrated anti-tumor effects against tumor advancement of S-180 2. SKH and SKB showed on elevation of macrophage for tumor-bearing mice. 3. $100{\mu}g/ml,\;500{\mu}g/ml$ of SKH and $500{\mu}g/ml$ of SKB demonstrated a rise in alkaline phosphates of B-Lymphocyte in the spleen in tumor-bearing mice. Results support a role for both SKH and SKB for anti-tumor effects via endorsement of macrophage and encouragement of B-lymphocyte toward S-180.

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Lumbar Spinal Extradural Angiolipoma : Case Report and Review of the Literature

  • Park, Jin-Hoon;Jeon, Sang-Ryong;Rhim, Seung-Chul;Roh, Sung-Woo
    • Journal of Korean Neurosurgical Society
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    • v.44 no.4
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    • pp.265-267
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    • 2008
  • Angiolipomas in the lumbar spinal region are extremely rare. The present report describes the identification of such a tumor and its removal, and discusses the tumor characteristics and prognosis. A 74-year-old woman was presented with a 5-month history of lower back pain. Severe radiculopathy was experienced in the left leg for 5 days prior to the presentation, and there were no neurological deficits. Magnetic resonance (MR) images showed an approximately 3.5 cm heterogeneously enhanced and elongated mass at the left L5-S1 level. A portion of the mass appeared with high signal intensity on T2-weighted MR images, with low signal intensity on T1-weighted images, and with high signal intensity on T1 fat suppression enhancement images. Resection of the tumor was approached via an L5 and S1 laminectomy. A fibrous sticky yellowish hypervascular tumor was identified. Histological study revealed the tumor as an angiolipoma. Symptoms were relieved after tumor excision, and there were no neurological sequelae. Although extremely rare, lumbar epidural angiolipoma should be considered in the differential diagnosis of lumbar spinal epidural lesions. The prognosis after surgical management of this lesion is favorable.

Nrf2 in TIME: The Emerging Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Tumor Immune Microenvironment

  • Jialin Feng;Oliver J. Read;Albena T. Dinkova-Kostova
    • Molecules and Cells
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    • v.46 no.3
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    • pp.142-152
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    • 2023
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.

Nuclear Localization of Chfr Is Crucial for Its Checkpoint Function

  • Kwon, Young Eun;Kim, Ye Seul;Oh, Young Mi;Seol, Jae Hong
    • Molecules and Cells
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    • v.27 no.3
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    • pp.359-363
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    • 2009
  • Chfr, a checkpoint with FHA and RING finger domains, plays an important role in cell cycle progression and tumor suppression. Chfr possesses the E3 ubiquitin ligase activity and stimulates the formation of polyubiquitin chains by Ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins, including Plk1 and Aurora A. While Chfr is a nuclear protein that functions within the cell nucleus, how Chfr is localized in the nucleus has not been clearly demonstrated. Here, we show that nuclear localization of Chfr is mediated by nuclear localization signal (NLS) sequences. To reveal the signal sequences responsible for nuclear localization, a short lysine-rich stretch (KKK) at amino acid residues 257-259 was replaced with alanine, which completely abolished nuclear localization. Moreover, we show that nuclear localization of Chfr is essential for its checkpoint function but not for its stability. Thus, our results suggest that NLS-mediated nuclear localization of Chfr leads to its accumulation within the nucleus, which may be important in the regulation of Chfr activation and Chfr-mediated cellular processes, including cell cycle progression and tumor suppression.

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

  • Prabhu, Venugopal Vinod;Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekharan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6215-6220
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    • 2013
  • Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers.

The Phosphorylation Status of Merlin Is Important for Regulating the Ras-ERK Pathway

  • Jung, Ju Ri;Kim, Hongtae;Jeun, Sin-Soo;Lee, Joo Yong;Koh, Eun-Jeoung;Ji, Cheol
    • Molecules and Cells
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    • v.20 no.2
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    • pp.196-200
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    • 2005
  • The neurofibromatosis type2 (NF2) tumor suppressor gene product, merlin, is structurally related to the ezrin-radixin-moesin (ERM) family of proteins that anchor the actin cytoskeleton to specific membrane proteins and participate in cell signaling. However, the basis of the tumor suppressing activity of merlin is not well understood. Previously, we identified a role of merlin as an inhibitor of the Ras-ERK signaling pathway. Recent studies have suggested that phosphorylation of merlin, as of other ERM proteins, may regulate its function. To determine whether phosphorylation of merlin affects its suppression of Ras-ERK signaling, we generated plasmids expressing full-length merlin with substitutions of serine 518, a potential phosphorylation site. A substitution that mimics constitutive phosphorylation (S518D) abrogated the ability of merlin to suppress effects of the Ras-ERK signaling pathway such as Ras-induced SRE transactivation, Elk-mediated SRE transactivation, Ras-induced ERK phosphorylation and Ras-induced focus formation. On the other hand, an S518A mutant, which mimics nonphosphorylated merlin, acted like wild type merlin. These observations show that mimicking merlin phosphorylation impairs not only growth suppression by merlin but also its inhibitory action on the Ras-ERK signaling pathway.