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Reprogramming of CaCo2 colorectal cancer cells after using the complex of poly-(N-vinylpyrrolidone) with small

Oxana V Klimenko1, Mikhail Shtilman2

  • 1SID ALEX GROUP, LTD, Kyselova, 1185/2, Prague, 182 00, Czechia.

Toxicology Reports
|March 23, 2019
PubMed

Insights

Researchers reprogrammed CaCo2 colorectal cancer cells into CD4+ cells using poly-(N-vinylpyrrolidone) (PVP) nanoparticles carrying specific small non-coding RNAs. This advancement offers potential for novel cancer therapies.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biotechnology

Background:

  • Small non-coding RNAs (ncRNAs) are crucial regulators of embryonic development and cellular differentiation.
  • Dysregulation of ncRNAs is implicated in various human diseases, driving research into ncRNA-based therapeutics.
  • Colorectal adenocarcinoma presents a significant health challenge, necessitating innovative treatment strategies.

Purpose of the Study:

  • To investigate the epigenetic reprogramming of CaCo2 colorectal adenocarcinoma cells.
  • To evaluate the transformation of CaCo2 cells into CD4+ cells using novel nanocarrier systems.
  • To assess the efficiency and duration of transfection by poly-(N-vinylpyrrolidone)/small non-coding RNA complexes.

Main Methods:

  • Epigenetic reprogramming of CaCo2 cells using nano-sized complexes of amphiphilic poly-(N-vinylpyrrolidone) (PVP) with miRNA-152 and piRNA-30074.
  • Confirmation of cell transformation through morphological and genetic analyses.
  • Detection of CD4+ lymphocytes marker via immunofluorescence.
  • Assessment of transfection efficiency and duration using fluorescence microscopy.

Main Results:

  • Successful epigenetic reprogramming and transformation of CaCo2 cells into CD4+ cells were achieved.
  • Morphological and genetic alterations confirmed the reprogramming dynamic.
  • Immunofluorescence validated the expression of the CD4+ lymphocytes marker.
  • The study characterized the transfection efficiency and duration of the PVP/ncRNA complexes in CaCo2 cells.

Conclusions:

  • Amphiphilic poly-(N-vinylpyrrolidone) nanoparticles effectively deliver small non-coding RNAs for cell reprogramming.
  • This method demonstrates potential for transforming cancer cells into a specific lineage, like CD4+ lymphocytes.
  • The findings support the development of novel ncRNA-based therapeutic approaches for colorectal cancer and other pathologies.
Keywords:
AGO2, argonaute 2Amphiphilic poly-(N-vinylpyrrolidone)BACH1, BTB domain and CNC homolog 1CD, cluster of differentiationCaCo2 colorectal adenocarcinomaDICER1, ribonuclease IIIDNMT1, DNA methyltransferase 1DTT, dithyothreitolERK1/2, extracellular signal regulated kinase ½FGF2, fibroblast growth factor 2GITR3A, glucocorticoid-induced TNFR-related proteinH3K9me3, tri-methyl lysine 9 of histone H3HILI, human piwiHMOX1, heme oxygenase 1HOXA10, homebox A10ICOS1B, inducible T-cell co-stimulatorIL, interleukinKIR1DL2, CD158b, expressed on natural killer cells and a subset of T cellsMKI-67, marker of proliferation ki-67OCT4, octamer-binding transcription factor 4PIWIL1, piwi-like protein 1PNVP, poly-(N-vinylpyrrolidone)Polymer carriersRB1, retinoblastoma 1ReprogrammingSncRNAs, small non-coding RNAsTE, transposon elementsTGFBR2, transforming growth factor beta receptor 2TNFRS6B, TNF receptor superfamily 6BTSS, transcriptional start sitesVMAF, musculoaponeurotic fibrosarcomaWnt-1, wingless type MMTV integration site family, member 1iPS, induced pluripotent stem cellsmTOR, mechanistic target of rapamycinmiR, micro-RNAmiRNA-152piR, piwi-interacting RNA, P-element induced wimpy testis interacting RNApiRNA-30074

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