Col1a1, encoding the type I collagen α1 chain, is a key member of the collagen family. Type I collagen is the most abundant collagen, playing essential roles in providing structural support to various tissues. It is involved in multiple biological processes such as epithelial-mesenchymal transition, which is closely linked to malignant tumorigenesis [1].

In malignancies, Col1a1 is highly expressed and regulates cell proliferation, metastasis, apoptosis, and cisplatin resistance [1]. For instance, in breast cancer, knockdown of Col1a1 inhibited metastasis independent of the epithelial-mesenchymal transition process, and its increased level was associated with poor survival, especially in ER+ patients [3]. In osteosarcoma, the circRNA hsa_circ_0020378 promotes osteosarcoma progression by downregulating miR-339-3p/Col1a1 expression [6]. In brain lower grade glioma, Col1a1 overexpression was correlated with overall survival, and its expression was positively correlated with immune cell infiltration [8]. Also, Col1a1-PDGFB fusion associated fibrosarcoma of the uterine corpus is an aggressive tumor with chemotherapy resistance and poor prognosis [4,7]. Moreover, the COL1A1 rs1800012 polymorphism is associated with osteoporosis or fracture risk [5]. Pathogenic variants in COL1A1 are involved in osteogenesis imperfecta and rarely, Ehlers-Danlos syndrome subtypes and their overlap syndromes [2].

In conclusion, Col1a1 is crucial for maintaining tissue structure and is deeply involved in multiple disease processes including cancer, osteoporosis, and connective tissue disorders. Functional studies, including those from potential gene-knockout models (not explicitly detailed in provided references but inferred from the nature of the research), help in understanding its role in these diseases, providing potential targets for treatment.