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Updated: Apr 23, 2026
Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
Expression of Indian hedgehog is negatively correlated with APC gene mutation in colorectal tumors
Xiangsheng Fu1, Lei Shi1, Wei Zhang1
1Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
Abstract:
The regulatory mechanism of Indian hedgehog (IHH) in colorectal carcinogenesis has not been elucidated. In the current study, the expression of IHH were investigated in 7 digestive tract cancer cell lines, and in 10 normal colorectal mucosas (NCs), 30 hyperplastic polyps (HPs), 35 colorectal adenomas (ADs), and 40 colorectal adenocarcinomas (CAs) by semi-quantitative RT-PCR and immunohistochemical staining. Moreover, the mutational status of adenomatous polyposis coli (APC) and β-catenin in these tumors were analyzed by direct sequencing. IHH mRNA was lost in the 4 colon cancer cell lines harboring APC mutation. IHH mRNA was significantly decreased in CAs (0.17 ± 0.22), compared with that in ADs (0.38 ± 0.35) and HPs (0.56 ± 0.38, P < 0.05). IHH protein was expressed at a very low level or absent in both ADs (7.51 ± 11.92) and CAs (5.15 ± 9.21) in comparison to that in HPs (19.47 ± 17.91) and NCs (42.40 ± 13.67, P < 0.05). Moreover, APC mutations were negatively correlated with IHH mRNA expression (Spearman's R = -0.636, P < 0.01) and IHH protein expression (Spearman's R = -0.426, P < 0.01). In conclusion, down-regulation of IHH expression might be an early event during the carcinogenesis of colorectal cancer. The activation of Wnt signaling by APC mutation might contribute to the down-regulation or loss of IHH expression in colorectal tumors.
Insights
Indian hedgehog (IHH) expression decreases during colorectal cancer development. APC mutations correlate with reduced IHH, suggesting IHH down-regulation is an early event in colorectal carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- The role of Indian hedgehog (IHH) in colorectal carcinogenesis remains unclear.
- Understanding IHH's regulatory mechanism is crucial for colorectal cancer research.
Purpose of the Study:
- To investigate the expression of Indian hedgehog (IHH) in various stages of colorectal neoplasia.
- To analyze the correlation between IHH expression and mutations in adenomatous polyposis coli (APC) and β-catenin.
Main Methods:
- Semi-quantitative RT-PCR and immunohistochemical staining were used to assess IHH expression.
- Direct sequencing was employed to determine the mutational status of APC and β-catenin.
- IHH expression was evaluated in normal colorectal mucosa, hyperplastic polyps, adenomas, and adenocarcinomas.
Main Results:
- IHH mRNA was lost in colon cancer cell lines with APC mutations.
- IHH mRNA and protein levels were significantly decreased in colorectal adenomas and adenocarcinomas compared to hyperplastic polyps and normal mucosa.
- APC mutations showed a negative correlation with both IHH mRNA and protein expression.
Conclusions:
- Down-regulation of IHH expression appears to be an early event in colorectal cancer development.
- Activation of Wnt signaling due to APC mutations may contribute to the loss or reduction of IHH expression in colorectal tumors.
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