Ldoc1, or leucine zipper downregulated in cancer 1, has been proposed as a regulator of transcription and cell signaling. It is involved in multiple pathways such as NF-κB, PI3K/Akt/GSK-3β, and Wnt/β -catenin, and is of great importance in cancer-related biological processes [3,4,5,7]. Genetic models could potentially help further elucidate its functions.

In vulvar carcinoma, high LDOC1 expression is associated with unfavorable overall and disease-free survival [1]. In oral squamous cell carcinoma (OSCC), salivary LDOC1 shows gender-different expression patterns and may serve as a biomarker [2]. In thyroid cancer, LDOC1 is downregulated in papillary thyroid carcinoma (PTC), and its overexpression suppresses the malignant phenotype, while ablation promotes it, with NF-κB inhibition reversing the effects of ablation [3,5]. In oral cells, LDOC1 suppresses microbe-induced production of IL-1β through the PI3K/Akt/GSK-3β axis [4]. In osteosarcoma, LDOC1 is a tumor suppressor that regulates metastasis and is correlated with patient survival [6]. In colorectal cancer, LDOC1 overexpression inhibits cell proliferation, migration, invasion, and promotes apoptosis by downregulating the Wnt/β-catenin pathway [7]. In oral neoplastic transformation, cigarette-induced promoter methylation may downregulate LDOC1, suggesting its tumor-suppressor role in smoking-related malignancies [8]. In chronic lymphocytic leukemia, LDOC1 expression is associated with somatic mutation status and can predict overall survival in untreated patients [9].

In conclusion, LDOC1 plays diverse roles in multiple biological processes, especially in cancer-related events. Its functions are closely related to various signaling pathways, and its abnormal expression is associated with different cancer types. The study of LDOC1 using different research models helps to understand its functions in disease occurrence and progression, potentially providing new therapeutic targets.

References:

1. Wanka, Giulia, Schmoeckel, Elisa, Mayr, Doris, Jeschke, Udo, Jueckstock, Julia. 2020. LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients. In International journal of molecular sciences, 21, . doi:10.3390/ijms21239287. https://pubmed.ncbi.nlm.nih.gov/33291445/

2. Liu, Chung-Ji, Chen, Jen-Hao, Hsia, Shih-Min, Shieh, Tzong-Ming, Shih, Yin-Hwa. 2019. Salivary LDOC1 is a gender-difference biomarker of oral squamous cell carcinoma. In PeerJ, 7, e6732. doi:10.7717/peerj.6732. https://pubmed.ncbi.nlm.nih.gov/30993049/

3. Zhao, Shuiying, Zhao, Yanyan, Wang, Qingzhu, Ji, Hongfei, Qin, Guijun. 2020. LDOC1 is differentially expressed in thyroid cancer and display tumor-suppressive function in papillary thyroid carcinoma. In Cell biology international, 44, 985-997. doi:10.1002/cbin.11295. https://pubmed.ncbi.nlm.nih.gov/31889386/

4. Lee, Chia-Huei, Hung, Pin-Feng, Liu, Ko-Jiunn, Yang, Ji-Rui, Yen, Ching-Yu. 2020. LDOC1 Suppresses Microbe-Induced Production of IL-1β in Human Normal and Cancerous Oral Cells through the PI3K/Akt/GSK-3β Axis. In Cancers, 12, . doi:10.3390/cancers12113148. https://pubmed.ncbi.nlm.nih.gov/33120999/

5. Zhao, Shuiying, Wang, Qingzhu, Li, Zhizhen, Ji, Hongfei, Qin, Guijun. 2015. LDOC1 inhibits proliferation and promotes apoptosis by repressing NF-κB activation in papillary thyroid carcinoma. In Journal of experimental & clinical cancer research : CR, 34, 146. doi:10.1186/s13046-015-0265-z. https://pubmed.ncbi.nlm.nih.gov/26637328/

6. Yong, Bi-Cheng, Lu, Jin-Chang, Xie, Xian-Biao, Xu, Hong-Wen, Shen, Jing-Nan. . LDOC1 regulates Wnt5a expression and osteosarcoma cell metastasis and is correlated with the survival of osteosarcoma patients. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 39, 1010428317691188. doi:10.1177/1010428317691188. https://pubmed.ncbi.nlm.nih.gov/28240050/

7. Jiang, Jiayi, Li, You, Jiang, Zheng. 2019. Effects of LDOC1 on colorectal cancer cells via downregulation of the Wnt/β-catenin signaling pathway. In Oncology reports, 41, 3281-3291. doi:10.3892/or.2019.7126. https://pubmed.ncbi.nlm.nih.gov/31002361/

8. Lee, Chia-Huei, Pan, Kao-Lu, Tang, Ya-Chu, Huang, Tze-Ta, Lin, Pinpin. . LDOC1 silenced by cigarette exposure and involved in oral neoplastic transformation. In Oncotarget, 6, 25188-201. doi:10.18632/oncotarget.4512. https://pubmed.ncbi.nlm.nih.gov/26317789/

9. Duzkale, Hatice, Schweighofer, Carmen D, Coombes, Kevin R, Keating, Michael J, Abruzzo, Lynne V. 2011. LDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and predicts overall survival in untreated patients. In Blood, 117, 4076-84. doi:10.1182/blood-2010-09-304881. https://pubmed.ncbi.nlm.nih.gov/21310924/