Htr1d, also known as 5-hydroxytryptamine receptor 1D, is a member of the serotonin receptor family. It is involved in multiple biological processes and is associated with the PI3K-AKT signaling pathway, which is crucial in cell growth, proliferation, and survival [1,2,3]. Htr1d has been shown to play important roles in various physiological and pathological conditions, highlighting its overall biological importance. Genetic models, such as gene knockout (KO) mouse models, can be valuable for studying its functions.

In pancreatic cancer, knocking down Htr1D inhibited the proliferation and migration of pancreatic cancer cells and promoted apoptosis by upregulating p-AKT, suggesting that the HOXA10-AS/miR-340-3p/HTR1D axis is crucial for the malignant biological behavior of pancreatic cancer [1]. In hepatocellular carcinoma, interference with Htr1D gene expression demonstrated its role in promoting HCC proliferation, migration, and drug resistance through the PI3K/Akt pathway, and it could be a valuable prognostic marker [2]. In gastric cancer, knockdown and inhibition of Htr1D impaired the proliferation and migration of gastric cancer cells [3].

In conclusion, Htr1d is involved in regulating cell proliferation, migration, and apoptosis through the PI3K-AKT signaling pathway in cancers such as pancreatic, hepatocellular, and gastric cancers. The use of KO mouse models and other loss-of-function experiments has provided insights into its role in these disease conditions, highlighting its potential as a therapeutic target in cancer treatment [1,2,3].

References:

1. Wu, Wu, Li, Qujin, Zhu, Zhu, Wang, Menghao, Gong, Jianping. 2022. HTR1D functions as a key target of HOXA10-AS/miR-340-3p axis to promote the malignant outcome of pancreatic cancer via PI3K-AKT signaling pathway. In International journal of biological sciences, 18, 3777-3794. doi:10.7150/ijbs.70546. https://pubmed.ncbi.nlm.nih.gov/35813473/

2. Zhang, Yingai, Zhang, Yuting, Zhou, Shuai, Zhang, Jianquan, Zhou, Hailong. 2025. HTR1D regulates the PI3K/Akt signaling pathway to impact hepatocellular carcinoma development and resistance to sorafenib. In BMC cancer, 25, 185. doi:10.1186/s12885-025-13575-5. https://pubmed.ncbi.nlm.nih.gov/39891115/

3. Jin, Xinghan, Li, Huan, Li, Bo, Zhang, Changhua, He, Yulong. 2022. Knockdown and inhibition of hydroxytryptamine receptor 1D suppress proliferation and migration of gastric cancer cells. In Biochemical and biophysical research communications, 620, 143-149. doi:10.1016/j.bbrc.2022.06.088. https://pubmed.ncbi.nlm.nih.gov/35785570/