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Titin as a potential novel therapeutic target in colorectal cancer |
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| Authors: | Hongyun Wei Keyu Ren Qian Zhang Yanchun Jin Bin Cao Zibin Tian Tao Mao Linlin Ren |
| Institution: | 1. Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China
Contribution: Formal analysis (lead), Funding acquisition (lead), Methodology (lead), Project administration (lead), Software (lead), Writing - original draft (lead);2. Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China Contribution: Software (equal), Writing - review & editing (supporting);3. Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China Contribution: Formal analysis (equal), Methodology (equal), Writing - original draft (supporting);4. Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China Contribution: Writing - original draft (supporting);5. Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China Contribution: Data curation (lead), Validation (lead), Writing - review & editing (equal);6. Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China Contribution: Conceptualization (equal), Data curation (supporting), Writing - review & editing (supporting);7. Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China |
| Abstract: | Colorectal cancer (CRC) is identified as a primary cause of death around the world. The current chemotherapies are not cost-effective. Therefore, finding novel potential therapeutic target is urgent. Titin (TTN) is a muscle protein that is critical in hypertrophic cardiomyopathy. However, its role in CRC is not well understood. The study focused on exploring the possible role of TTN in CRC carcinogenesis. TTN mRNA and protein expression levels presented an obvious downregulation in CRC tissue samples, relative to normal control (p < 0.05). TTN expression significantly correlated with the clinical stage (normal vs. Stage 1, p < 0.05; normal vs. Stage 4, p < 0.05), node metastasis (normal vs. N1, p < 0.05; N1 vs. N2, p < 0.05), histological type (normal vs. adenocarcinoma, p < 0.05), race (Caucasian vs. Asian, p < 0.05; African-American vs. Asian, p < 0.05) and TP53 mutation (normal vs. TP53 mutation, p < 0.05), considering The Cancer Genome Atlas database. However, for patients who had higher TTN expression, the overall survival was remarkably shorter than patients who had low TTN expression. Furthermore, TTN was lowly expressed in four CRC cell lines. TTN overexpression facilitated CRC cells in terms of the proliferation, metastasis and invasion. Based on gene set enrichment analysis, the ERB pathway might be responsible for TTN-related CRC. Besides, TTN was involved in the response to azacitidine. Overall, TTN might serve as a potential novel therapeutic target for treating and overcoming chemotherapy resistance in CRC. |
| Keywords: | colorectal cancer metastasis novel target proliferation titin |