Tgfb1i1, also known as TGF-β1 induced transcript 1 or Hic-5, is a cofactor of cellular TGF-β1. It interacts with various nuclear receptors and is involved in multiple biological processes. TGF-β1 signaling pathway, which Tgfb1i1 is associated with, plays a crucial role in cell growth, differentiation, and apoptosis. Tgfb1i1 is important in maintaining normal cellular functions and its dysregulation may lead to various diseases [1,4].

In urothelial carcinoma (UC), in vitro studies and analysis of clinicopathological data showed that overexpression of Tgfb1i1 was significantly correlated with advanced tumor stage. It regulates UC cell proliferation, viability, and induces epithelial-mesenchymal transition (EMT) to facilitate cell migration, promoting tumor aggressiveness in both upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC) [1].

In hypospadias, maternal exposure to dibutyl phthalate (DBP) suppresses Tgfb1i1, which impairs angiogenesis and the AR signalling pathway. Decreased Tgfb1i1 expression disrupted tube formation and migration in HUVECs, while overexpression promoted these processes [2].

In type II diabetes, upregulation of Tgfb1i1 in hepatic stellate cells (HSCs) exacerbated the development of metabolic-associated fatty liver disease (MAFLD) to steatohepatitis [3].

In bovine fetal ovaries, TGFβ1 increased the expression of Tgfb1i1 in ovarian fibroblasts, and changes in TGFβ signalling during fetal ovary development may be related to polycystic ovary syndrome (PCOS) [4].

In osteosarcoma, PTHR1 may be involved in its progression by regulating the miR-124-3p-AR-Tgfb1i1 axis [5].

In diabetes-mimicking conditions, ET-1 increased the expression of Tgfb1i1 in brain pericytes, triggering senescence and phenotypic changes [6].

In astrocytomas, TGFB1I1-induced EMT contributed to malignant progression [7].

In primary advanced colorectal cancer, the expression levels of TGFB1I1 may be potential biomarkers to predict the effects of FOLFOX4 chemotherapy [8].

TGFB1I1 is a novel marker for the smooth muscle contractile phenotype and is regulated by serum response factor/myocardin protein, and silencing of its expression promotes smooth muscle cell proliferation [9].

In bovine ovarian development, the expression of TGFB1I1 increased from the first trimester to the second and remained at that level in the third trimester, and it was part of the androgen and TGFβ signalling pathways [10].

In conclusion, Tgfb1i1 plays essential roles in multiple biological processes and disease conditions. Studies on Tgfb1i1 in various models have revealed its significance in cancer development such as in urothelial carcinoma and astrocytomas, as well as in non-cancerous diseases like hypospadias, type II diabetes, and potentially PCOS. These findings contribute to a better understanding of disease mechanisms and may provide potential targets for treatment.

References:

1. Liang, Peir-In, Wei, Yu-Ching, Chen, Huan-Da, Chien, Chu-Chun, Chuang, Hao-Wen. 2024. TGFB1I1 promotes cell proliferation and migration in urothelial carcinoma. In The Kaohsiung journal of medical sciences, 40, 269-279. doi:10.1002/kjm2.12798. https://pubmed.ncbi.nlm.nih.gov/38180299/

2. Wu, Lei, Shi, Fei, Zhang, Yongqing, Xia, Shujie, Jiang, Juntao. 2024. Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring. In Ecotoxicology and environmental safety, 270, 115941. doi:10.1016/j.ecoenv.2024.115941. https://pubmed.ncbi.nlm.nih.gov/38184977/

3. Dai, Chia-Yen, Tsai, Ying-Ming, Chang, Chao-Yuan, Sun, Chien-Hui, Hsu, Ya-Ling. 2024. Reconstruction of the Hepatic Microenvironment and Pathological Changes Underlying Type II Diabetes through Single-Cell RNA Sequencing. In International journal of biological sciences, 20, 5531-5547. doi:10.7150/ijbs.99176. https://pubmed.ncbi.nlm.nih.gov/39494341/

4. Azumah, Rafiatu, Liu, Menghe, Hummitzsch, Katja, Anderson, Richard A, Rodgers, Raymond J. . Candidate genes for polycystic ovary syndrome are regulated by TGFβ in the bovine foetal ovary. In Human reproduction (Oxford, England), 37, 1244-1254. doi:10.1093/humrep/deac049. https://pubmed.ncbi.nlm.nih.gov/35413103/

5. Li, Shenglong, Wu, Xixi, Pei, Yi, Qiu, Enduo, Zhang, Xiaojing. 2019. PTHR1 May Be Involved in Progression of Osteosarcoma by Regulating miR-124-3p-AR-Tgfb1i1, miR-27a-3p-PPARG-Abca1, and miR-103/590-3p-AXIN2 Axes. In DNA and cell biology, 38, 1323-1337. doi:10.1089/dna.2019.4880. https://pubmed.ncbi.nlm.nih.gov/31536386/

6. Edgerton-Fulton, Mia, Abdul, Yasir, Jamil, Sarah, Ergul, Adviye. . Endothelin-1 (ET-1) contributes to senescence and phenotypic changes in brain pericytes in diabetes-mimicking conditions. In Clinical science (London, England : 1979), 138, 1009-1022. doi:10.1042/CS20240328. https://pubmed.ncbi.nlm.nih.gov/39106080/

7. Liu, Yanwei, Hu, Huimin, Wang, Kuanyu, Zhang, Wei, Jiang, Tao. . Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas. In Oncotarget, 5, 12593-606. doi:. https://pubmed.ncbi.nlm.nih.gov/25333259/

8. Li, Shaotang, Lu, Xingrong, Chi, Pan, Pan, Jie. 2012. Identification of Nkx2-3 and TGFB1I1 expression levels as potential biomarkers to predict the effects of FOLFOX4 chemotherapy. In Cancer biology & therapy, 13, 443-9. doi:10.4161/cbt.19298. https://pubmed.ncbi.nlm.nih.gov/22313639/

9. Wang, Xiaobo, Hu, Guoqing, Betts, Courtney, Van De Water, Livingston, Zhou, Jiliang. 2011. Transforming growth factor-β1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein. In The Journal of biological chemistry, 286, 41589-41599. doi:10.1074/jbc.M111.250878. https://pubmed.ncbi.nlm.nih.gov/21984848/

10. Hatzirodos, Nicholas, Hummitzsch, Katja, Irving-Rodgers, Helen F, Anderson, Richard A, Rodgers, Raymond J. 2019. Transcript abundance of stromal and thecal cell related genes during bovine ovarian development. In PloS one, 14, e0213575. doi:10.1371/journal.pone.0213575. https://pubmed.ncbi.nlm.nih.gov/30856218/