Knockdown of long non‑coding RNA PVT1 reverses multidrug resistance in colorectal cancer cells

Heng Fan1, Jian-Hua Zhu2, Xue-Qing Yao1

  • 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Insights

Plasmacytoma variant translocation 1 (PVT1) is highly expressed in multidrug-resistant colorectal cancer (CRC). Inhibiting PVT1 may reverse 5-fluorouracil resistance in CRC, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Multidrug resistance (MDR) is a major challenge in colorectal cancer (CRC) chemotherapy.
  • Plasmacytoma variant translocation 1 (PVT1) is linked to poor survival in CRC patients.
  • The role of PVT1 in CRC MDR is not fully understood.

Purpose of the Study:

  • To investigate the association between PVT1 expression and 5-fluorouracil (5-FU) resistance in colorectal cancer.
  • To determine if PVT1 plays a critical role in mediating MDR in CRC cells.

Main Methods:

  • Assessed PVT1 mRNA levels in 5-FU-resistant CRC tissues and cell lines using RT-qPCR.
  • Evaluated cytotoxicity via Cell Counting Kit-8 assay and apoptosis rates using flow cytometry.
  • Manipulated PVT1 expression (siRNA knockdown and overexpression) in CRC cell lines.

Main Results:

  • PVT1 mRNA was significantly upregulated in 5-FU-resistant CRC tissues and cell lines.
  • PVT1 knockdown increased apoptosis and decreased survival in 5-FU-treated CRC cells.
  • PVT1 overexpression decreased apoptosis and increased survival in 5-FU-treated CRC cells, upregulating MDR-associated proteins (MRP1, P-gp) and mTOR/Bcl2.

Conclusions:

  • PVT1 overexpression promotes MDR in colorectal cancer cells.
  • Inhibition of PVT1 may serve as a therapeutic strategy to overcome 5-FU resistance in CRC.

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