4.6 Article

The circRNA expression profile of colorectal inflammatory cancer transformation revealed potential predictive biomarkers

Journal

AGING-US
Volume 14, Issue 22, Pages 9280-9299

Publisher

IMPACT JOURNALS LLC

Keywords

colorectal cancer; colorectal adenoma; circular RNAs (circRNAs); inflammatory cancer transformation; RNA sequencing; biomarkers

Funding

  1. National Nature Science Foundation of China [82104466]
  2. Shanghai Frontier Research Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation [2021KJ03-12]
  3. Shanghai Rising-Star Program [20QA1409300]
  4. Program for Young Eastern Scholar at Shanghai Institutions of Higher Learning [QD2019034]
  5. Health Science and Technology project of Shanghai Pudong New Area Health Commission [PW2021A-43]
  6. Shanghai Pudong New Area Health System discipline leader Training Program [PWRd2021-21]
  7. scientific research project of Shanghai Pudong New Area Science and Technology Development Fund [PKJ2019Y17]

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This study investigated the relationship between circRNA and the malignant transformation from colorectal adenoma to colorectal cancer, and identified potential biomarkers for the early diagnosis of colorectal cancer.
Colorectal cancer (CRC) is one of the most common malignant tumors in the world, and most colorectal cancer is transformed from colorectal adenoma (CRA). Identifying biomarkers for the early prediction of colorectal cancer would be an important finding. Circular RNA (circRNA) plays a key role in the occurrence and development of tumors, and its biological characteristics make it a potential biomarker for the early diagnosis of diseases. Therefore, we explored the relationship between circRNA and the malignant transformation from colorectal adenoma to colorectal cancer. We constructed inflammation-based tumorigenesis mouse models and performed high-throughput RNA sequencing to determine the expression profile of circRNAs in tissues at different stages of disease. Subsequent STEM analysis showed that with the development of the disease, 30 circRNAs were significantly downregulated, and 10 circRNAs were significantly upregulated. After qRT-PCR and Fish analysis verification, it was clear that mmu_circ_0008035 and mmu_circ_0000420 were significantly and continuously overexpressed in the development of colorectal cancer in our mouse model. Next, through homology analysis of circRNA in human and mouse and validation of clinical normal tissues, adenoma tissues and CRC tissues, we found biomarkers of has_circ0101338 ahashsa_circ0022426 that could predict the malignant transformation of human colorectal inflammation into CRC and have certain diagnostic value. In conclusion, our results may shed light on the mechanism of progression from precancerous adenoma to cancer and provide biomarkers that may be used in the early diagnosis of CRC.

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