Downregulation of Sec23A protein by miRNA-375 in prostate carcinoma

Jaroslaw Szczyrba1, Elke Nolte, Sven Wach

  • 1Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Virologie, Haus 47, Universitätsklinikum, 66421 Homburg/Saar, Germany.

Insights

MicroRNAs miR-375 and miR-200c target SEC23A in prostate cancer. Overexpression of miR-375 correlates with reduced SEC23A, impacting cancer cell growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate carcinoma (CaP) is a significant cause of cancer-related mortality in men.
  • MicroRNAs (miRNAs) are key regulators of gene expression, influencing various cellular processes.
  • Previous studies identified altered miRNA profiles in primary CaP.

Purpose of the Study:

  • To investigate the regulatory role of miR-375 and miR-200c on SEC23A in prostate cancer.
  • To determine the correlation between SEC23A expression and specific miRNAs in CaP.
  • To evaluate the impact of Sec23A on prostate cancer cell growth.

Main Methods:

  • miRNA sequencing and computational analysis to identify potential miRNA targets.
  • Validation of SEC23A as a target for miR-375 and miR-200c using cell-based assays.
  • Correlation analysis of miRNA and SEC23A mRNA/protein levels in CaP tissues and cell lines.
  • Assessment of Sec23A's effect on CaP cell proliferation and apoptosis.

Main Results:

  • The 3'-untranslated region (3'-UTR) of SEC23A mRNA was confirmed as a target for miR-375 and miR-200c.
  • Both miRNAs were found to downregulate Sec23A protein expression.
  • A negative correlation was observed between miR-375 and SEC23A mRNA in primary CaP.
  • Reduced Sec23A protein levels were inversely correlated with increased miR-375 in CaP cell lines and tissues.
  • Overexpression of Sec23A inhibited CaP cell growth, while its inhibition stimulated proliferation.

Conclusions:

  • miR-375 and miR-200c directly target SEC23A, downregulating its protein expression in prostate cancer.
  • miR-375's upregulation is associated with decreased SEC23A levels in CaP.
  • Sec23A plays a role in regulating prostate cancer cell proliferation, suggesting its potential as a therapeutic target.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...