Tnnc1, which encodes troponin C type 1, is a gene with significant importance. The protein it encodes is a calcium-sensing component in the troponin complex of striated muscle, playing a crucial role in regulating muscle contraction in a calcium-dependent manner [7]. It is involved in the calcium-mediated signaling pathway related to muscle function, and its proper function is essential for normal cardiac and slow-twitch skeletal muscle activities.

In genetic disease research, variants in TNNC1 have been associated with various cardiomyopathies. In dilated cardiomyopathy (DCM), TNNC1 variants were significantly enriched in specific patient subsets, potentially explaining a portion of DCM cases [1]. It was also classified as having definitive evidence of a monogenic relationship with idiopathic DCM [3]. In addition, TNNC1 mutations were associated with autosomal recessive restrictive cardiomyopathy with fatal outcomes in infancy [5]. In cancer research, TNNC1 knockout in ovarian cancer cells reversed their metastatic potential by inactivating epithelial-mesenchymal transition and suppressing F-actin polymerization [2]. In nonsmall-cell lung cancer, TNNC1 reduced gemcitabine sensitivity by increasing autophagy [4], while in lung adenocarcinoma, it was characterized as a novel tumor suppressor [6].

In conclusion, TNNC1 is essential for muscle contraction regulation. Its study through genetic models has revealed its roles in multiple disease areas. In cardiomyopathies, it is implicated in the genetic etiology, and in cancers, it influences metastatic potential, drug sensitivity, and tumor suppression, highlighting its significance in understanding disease mechanisms and potentially developing targeted therapies.

References:

1. Mazzarotto, Francesco, Tayal, Upasana, Buchan, Rachel J, Ware, James S, Walsh, Roddy. 2020. Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy. In Circulation, 141, 387-398. doi:10.1161/CIRCULATIONAHA.119.037661. https://pubmed.ncbi.nlm.nih.gov/31983221/

2. Yin, Jing Hu, Elumalai, Perumal, Kim, So Youn, Lee, Minho, Chung, Yeun-Jun. 2021. TNNC1 knockout reverses metastatic potential of ovarian cancer cells by inactivating epithelial-mesenchymal transition and suppressing F-actin polymerization. In Biochemical and biophysical research communications, 547, 44-51. doi:10.1016/j.bbrc.2021.02.021. https://pubmed.ncbi.nlm.nih.gov/33592378/

3. Jordan, Elizabeth, Peterson, Laiken, Ai, Tomohiko, Ware, James, Hershberger, Ray E. 2021. Evidence-Based Assessment of Genes in Dilated Cardiomyopathy. In Circulation, 144, 7-19. doi:10.1161/CIRCULATIONAHA.120.053033. https://pubmed.ncbi.nlm.nih.gov/33947203/

4. Ye, Xian, Xie, Guanghui, Liu, Zhijian, Guo, Chi, Tang, Jianfeng. 2020. TNNC1 Reduced Gemcitabine Sensitivity of Nonsmall-Cell Lung Cancer by Increasing Autophagy. In Medical science monitor : international medical journal of experimental and clinical research, 26, e922703. doi:10.12659/MSM.922703. https://pubmed.ncbi.nlm.nih.gov/32946432/

5. Ploski, Rafal, Rydzanicz, Malgorzata, Ksiazczyk, Tomasz M, Bilinska, Zofia T, Werner, Bozena. 2016. Evidence for troponin C (TNNC1) as a gene for autosomal recessive restrictive cardiomyopathy with fatal outcome in infancy. In American journal of medical genetics. Part A, 170, 3241-3248. doi:10.1002/ajmg.a.37860. https://pubmed.ncbi.nlm.nih.gov/27604170/

6. Kim, Suyeon, Kim, Jaewon, Jung, Yeonjoo, Lee, Sanghyuk, Kim, Jaesang. . Characterization of TNNC1 as a Novel Tumor Suppressor of Lung Adenocarcinoma. In Molecules and cells, 43, 619-631. doi:10.14348/molcells.2020.0075. https://pubmed.ncbi.nlm.nih.gov/32638704/

7. Li, Monica X, Hwang, Peter M. 2015. Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs. In Gene, 571, 153-66. doi:10.1016/j.gene.2015.07.074. https://pubmed.ncbi.nlm.nih.gov/26232335/