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lncRNA - Long Non-coding RNAs02:39

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
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The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
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LASP-1: a nuclear hub for the UHRF1-DNMT1-G9a-Snail1 complex.

N Duvall-Noelle1, A Karwandyar1, A Richmond1,2

  • 1Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN, USA.

Oncogene
|May 19, 2015
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Summary
This summary is machine-generated.

Nuclear LIM and SH3 protein-1 (LASP-1) is highly expressed in aggressive breast cancer. Tumor microenvironment signals trigger LASP-1 nuclear import, linking it to epigenetic machinery and altered cell behavior, impacting patient survival.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Nuclear LIM and SH3 protein-1 (LASP-1) expression correlates with breast cancer survival.
  • LASP-1 is absent in normal breast epithelium but highly nuclear in aggressive cancers.

Purpose of the Study:

  • To investigate if tumor microenvironment factors trigger nuclear translocation of LASP-1.
  • To elucidate the functional role of nuclear LASP-1 in breast cancer progression.

Main Methods:

  • Immunohistochemistry on human breast tissue microarrays.
  • Treatment of breast cancer cells with chemokines (CXCL12, CXCL8) and growth factors (EGF, HRG).
  • Biochemical fractionation, gene expression analysis, 3D cell culture, proteomics, and immunoprecipitation assays.

Main Results:

  • Chemokines and growth factors induced nuclear translocation of LASP-1, blocked by CXCR4 antagonist AMD-3100.
  • LASP-1 knockdown altered gene expression, cell-matrix interactions, and colony morphology.
  • LASP-1 associates with epigenetic regulators (UHRF1, DNMT1, G9a) and Snail1, particularly in response to CXCL12.

Conclusions:

  • Nuclear LASP-1 acts as a hub for epigenetic machinery in breast cancer.
  • CXCL12-induced nuclear import of LASP-1 influences epigenetic regulation and cancer cell behavior.
  • LASP-1's role in epigenetic regulation presents potential therapeutic targets for breast cancer.