• Title/Summary/Keyword: target mimicry

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Angiogenesis and vasculogenic mimicry as therapeutic targets in ovarian cancer

  • Lim, Dansaem;Do, Yeojin;Kwon, Byung Su;Chang, Woochul;Lee, Myeong-Sok;Kim, Jongmin;Cho, Jin Gu
    • BMB Reports
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    • v.53 no.6
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    • pp.291-298
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    • 2020
  • Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer.

Regulation of IL-6 signaling by miR-125a and let-7e in endothelial cells controls vasculogenic mimicry formation of breast cancer cells

  • Park, Youngsook;Kim, Jongmin
    • BMB Reports
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    • v.52 no.3
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    • pp.214-219
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    • 2019
  • The role of tumor-proximal factors in tumor plasticity during chemoresistance and metastasis following chemotherapy is well studied. However, the role of endothelial cell (EC) derived paracrine factors in tumor plasticity, their effect on chemotherapeutic outcome, and the mechanism by which these paracrine factors modulate the tumor microenvironment are not well understood. In this study, we report a novel mechanism by which endothelial miR-125a and let-7e-mediated regulation of interleukin-6 (IL-6) signaling can manipulate vasculogenic mimicry (VM) formation of MDA-MB-231 breast cancer cells. We found that endothelial IL-6 levels were significantly higher in response to cisplatin treatment, whereas levels of IL-6 upon cisplatin exposure remained unchanged in MDA-MB-231 breast cancer cells. We additionally found an inverse correlation between IL-6 and miR-125a/let-7e expression levels in cisplatin treated ECs. Interestingly, IL-6, IL-6 receptor (IL-6R), and signal transducer and activator of transcription 3 (STAT3) genes in the IL-6 pathway are closely regulated by miR-125a and let-7e, which directly target its 3' untranslated region. Functional analyses revealed that endothelial miR-125a and let-7e inhibit IL-6-induced adhesion of monocytes to ECs. Furthermore, conditioned medium from cisplatin treated ECs induced a significantly higher formation of VM in MDA-MB-231 breast cancer cells as compared to that from intact ECs; this effect of cisplatin treatment was abrogated by concurrent overexpression of miR-125a and let-7e. Overall, this study reveals a novel EC-tumor cell crosstalk mediated by the endothelial miR-125a/let-7e-IL-6 signaling axis, which might improve chemosensitivity and provide potential therapeutic targets for the treatment of cancer.

The continuous or categorical effects for HH vs. HL and HH vs. LH in lexical pitch accent contrasts of Korean

  • Kim, Jungsun
    • Phonetics and Speech Sciences
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    • v.6 no.4
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    • pp.53-65
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    • 2014
  • The current research examines whether pitch contour shapes in North Kyungsang pitch accent contrasts provide a phonetic dimension for phonological discreteness in a mimicry task. Two pitch accent continua resynthesized were created for HH vs. HL and HH vs. LH. To confirm a phonetic dimension for accounting for pitch accent categories in North Kyungsang Korean, the mimicries of speakers of two dialects (i.e., North Kyungsang & South Cholla) were compared. One of the findings showed that, for North Kyungsang speakers, the range of mean f0 peak times was a phonetic dimension undergoing a continuous shift within a stimulus continuum for both HH vs. HL and HH vs. LH. On the other hand, for South Cholla speakers, there were no apparent shifts around categorical boundaries for either HH vs. HL or HH vs. LH. Regarding individual mimicries on f0 peak timing, there are many variations. For HH vs. LH, three North Kyungsang speakers showed a discrete pattern reflecting a shift in phonological categories, but for HH vs. HL, there was no such distinction showing a categorical shift, though there were statistically significant differences for two speakers. Interestingly, one of the North Kyungsang speakers showed a continuous phonetic dimension for both HH vs. HL and HH vs. LH. Lastly, the f0 valley timing did not exhibit a discrete or gradient phonetic dimension for speakers of either dialect. On the basis of these results, what is interesting is that the tonal target such as high tone in North Kyungsang pitch accent categories within the autosegmental-metrical (AM) theory may be realized within individual cognitive systems for representing the interaction of perception and production.

The Biological Functions of Plant Long Noncoding RNAs (식물의 긴비암호화 RNA들의 생물학적 기능)

  • Kim, Jee Hye;Heo, Jae Bok
    • Journal of Life Science
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    • v.26 no.9
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    • pp.1097-1104
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    • 2016
  • With the development of next generation sequencing (NGS), large numbers of transcriptional molecules have been discovered. Most transcripts are non -coding RNAs (ncRNAs). Among them, long non-coding RNAs (lncRNAs) with more than 200 nucleotides represent functional RNA molecule that will not be translated into protein. In plants, lncRNAs are transcribed by RNA polymerase II (Pol II) or Pol III, Pol VI and Pol V. After transcription of these lncRNAs, more RNA processing mechanisms such as splicing and polyadenylation occurs. The expression of plant lncRNAs is very low and is tissue specific. However, these lncRNAs are strongly induced by specific external stimuli. Because different external stimuli including environmental stresses induce a large number of plant lncRNAs, these lncRNAs have been gradually considered as new regulatory factors of various biological and development processes such as epigenetic repression, chromatin modification, target mimicry, photomorphogenesis, protein relocalization, environmental stress response, pathogen infection in plants. Moreover, some lncRNAs act as precursor of short RNAs. Although a large number of lncRNAs have been predicted and identified in plants, our current understanding of the biological function of these lncRNAs is still limited and their detailed regulatory mechanisms should be elucidated continuously. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the molecular functions unraveled in plants.