{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTDRG1 was first identified as a testis‐specific gene with a pivotal role in spermatogenesis and mature sperm function. It is predominantly expressed in spermatogenic cells and persists in mature spermatozoa—localizing to structures such as the midpiece and flagellum—suggesting regulatory functions in sperm motility and potentially in testicular malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn reproductive system cancers, aberrant overexpression of TDRG1 has been implicated in promoting oncogenic behaviors. In endometrial carcinoma, increased TDRG1 levels boost cell viability, invasion, and migration while concurrently inhibiting apoptosis through its direct binding to VEGF-A and the activation of downstream effectors such as PI3K, Bcl-2, and MMP2. Similarly, in epithelial ovarian carcinoma, TDRG1 overexpression enhances proliferation and metastasis by suppressing miR-93, which in turn modulates molecules including RhoC and MMP2. In cervical cancer, TDRG1 functions as a competing endogenous RNA (ceRNA) that sequesters miR-214-5p to derepress SOX4, thereby promoting proliferation, migration, invasion, and epithelial–mesenchymal transition; its elevated expression even correlates with advanced disease stage and poorer patient prognosis. Notably, although one study noted that TDRG1 was recently identified in cervical cancer and suggested its general pro-carcinogenic potential, its precise role in this context continues to be refined."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond reproductive tissues, TDRG1 is emerging as an important modulator in a spectrum of other malignancies. In seminoma cells, its overexpression enhances autophagy via the activation of the p110β/Rab5/Vps34 pathway, contributing to cisplatin resistance. In non-small cell lung cancer, TDRG1 promotes proliferation and metastasis by sponging miR-873-5p, which increases the levels of the transcription factor ZEB1. In gastric carcinoma, elevated TDRG1 facilitates tumor growth and metastasis through a miR-873-5p/hepatoma-derived growth factor axis. Similarly, in breast cancer, TDRG1 acts as a molecular sponge for miR-214-5p, leading to the upregulation of CLIC4 and the promotion of proliferative and invasive cell behaviors. Moreover, in lung cancer stem cells, TDRG1 contributes to the maintenance and enhancement of stemness by binding to and stabilizing Sox2 mRNA."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its oncogenic roles, TDRG1 has been linked to non-neoplastic pathologies. In preeclampsia, TDRG1 is significantly downregulated in the placenta, and its reduced expression is associated with impaired trophoblast proliferation, migration, invasion, and cell cycle progression through a mechanism involving the sequestration of miR-214-5p and consequent modulation of Notch pathway components such as Jagged1 and Notch1. Furthermore, in the context of heart failure, TDRG1 exacerbates fibrogenesis and inflammatory responses in TGF-β1-stimulated human cardiac fibroblasts via binding to miR-605-3p and subsequent alterations in the expression of TNFRSF21, thereby contributing to adverse cardiac remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xianzhen Jiang, Dongjie Li, Jianfu Yang, et al. 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