2. Academic Validation
  3. POLQ knockdown inhibits proliferation, migration, and invasion by inducing cell cycle arrest in colorectal cancer

POLQ knockdown inhibits proliferation, migration, and invasion by inducing cell cycle arrest in colorectal cancer

  • Discov Oncol. 2024 Nov 9;15(1):633. doi: 10.1007/s12672-024-01496-x.
Qing Yao # 1 2 3 4,  Shuyang Gao # 1 2 3 4,  Qiannan Sun # 2 4 5,  Liuhua Wang 2 3 4,  Jun Ren 2 3 4,  Daorong Wang 6 7 8 9
Affiliations

Affiliations

  • 1 The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, 225001, China.
  • 2 Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
  • 3 General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China.
  • 4 Yangzhou, Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic, Yangzhou, 225001, China.
  • 5 Medical Research Center of Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
  • 6 The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, 225001, China. wdaorong666@sina.com.
  • 7 Northern Jiangsu People's Hospital, Yangzhou, 225001, China. wdaorong666@sina.com.
  • 8 General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China. wdaorong666@sina.com.
  • 9 Yangzhou, Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic, Yangzhou, 225001, China. wdaorong666@sina.com.
  • # Contributed equally.
PMID: 39520627 DOI: 10.1007/s12672-024-01496-x
Abstract

Background: Polymerase θ (POLQ) is an error-prone translesion synthesis polymerase that participates in the repair of DNA double-strand breaks. Previous studies have reported that the level of POLQ expression is distinctly upregulated in colorectal Cancer (CRC), but little attention has been given to its function and regulation of CRC progression. This study aimed to explore the specific function of POLQ in CRC.

Methods: Quantitative Real-Time PCR and western blotting analysis were used to assess the transcription and translation levels of POLQ. Then, POLQ was stably silenced using small interfering RNA in SW480 and HCT116 cells. Afterwards, the function of POLQ in CRC cells was proven via Cell Counting Kit‑8, scratch wound healing, colony formation, and Boyden chamber assays. Furthermore, we investigated the effects of POLQ on the cell cycle signaling pathway that obtained from biological pathway enrichment analysis and further verified by activating the signaling pathway.

Results: The results showed that POLQ was highly expressed in CRC tissues and cells and was associated with poor clinical outcomes of patients. Knockdown of POLQ significantly reduced the proliferation, migration and invasion of CRC cells. Additionally, POLQ knockdown markedly decreased the expression levels of MMP2 and MMP9, and blocked cell cycle progression by inhibiting the expression of G1/M and S/M phases proteins.

Conclusions: POLQ knockdown restrained the progression of CRC by blocking the cell cycle signaling pathway.

Keywords

Cell cycle signaling pathway; Colorectal cancer; DNA replication; Polymerase θ.

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