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Circ-CUL2/microRNA-888-5p/RB1CC1 axis participates in cisplatin resistance in NSCLC via repressing cell advancement

HengQi Chen1, Fang Li1, Qi Xue1

  • 1Deparment of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China.

Bioengineered
|January 24, 2022
PubMed

Insights

Circular RNA CUL2 (circ-CUL2) acts as a tumor suppressor in non-small cell lung cancer (NSCLC). It enhances cisplatin sensitivity by regulating the miR-888-5p/RB1CC1 axis, offering a new therapeutic strategy for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (circRNAs) play significant roles in human tumor progression and chemotherapy resistance.
  • Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
  • Understanding the specific functions of circRNAs in NSCLC is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the role of circ-CUL2 in the development and cisplatin resistance of non-small cell lung cancer (NSCLC).
  • To elucidate the molecular mechanism underlying the function of circ-CUL2 in NSCLC, focusing on the circ-CUL2/miR-888-5p/RB1CC1 axis.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were used to assess the expression levels of circ-CUL2, miR-888-5p, and RB1CC1 in NSCLC tissues and cell lines.
  • Cell counting kit (CCK)-8, plate clone, Transwell assays, and flow cytometry were employed to evaluate the effects of circ-CUL2 on NSCLC cell proliferation, migration, invasion, apoptosis, and cisplatin (DDP) resistance.
  • Bioinformatic analysis and dual-luciferase reporter assays were utilized to confirm the interaction between circ-CUL2, miR-888-5p, and RB1CC1.

Main Results:

  • Circ-CUL2 and RB1CC1 were found to be significantly downregulated in NSCLC tissues and cell lines, whereas miR-888-5p was upregulated.
  • Overexpression of circ-CUL2 or inhibition of miR-888-5p suppressed NSCLC cell proliferation, migration, and invasion, while promoting apoptosis and enhancing sensitivity to cisplatin.
  • Circ-CUL2 directly targets miR-888-5p, and miR-888-5p targets RB1CC1. Silencing RB1CC1 reversed the inhibitory effects of circ-CUL2 on NSCLC progression.

Conclusions:

  • Circ-CUL2 functions as an anti-tumor factor in NSCLC by modulating the circ-CUL2/miR-888-5p/RB1CC1 axis.
  • Circ-CUL2 enhances the sensitivity of NSCLC cells, including A549/DDP cells, to cisplatin.
  • Circ-CUL2 represents a potential novel biomarker and therapeutic target for NSCLC treatment.
Keywords:
Circular CUL2Circular RNANon-small cell lung cancerRB1CC1microRNA-888-5p

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