RETRACTED: Cyclin-dependent kinase 7 (CDK7) is an emerging prognostic biomarker and therapeutic target in osteosarcoma

Abstract

Background: Overexpression of cyclin-dependent kinase 7 (CDK7) is a well-known pathogenic feature of various malignancies and a sign of a more dismal prognosis. As relatively little is known about CDK7 in osteosarcoma, we elected to evaluate its expression, prognostic value, and function. Methods: We began by analyzing the publicly available data sets on CDK7 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2). The correlation between patient tissue CDK7 expression and their clinicopathological features and prognosis was assessed via immunohistochemical staining of a unique tissue microarray constructed from osteosarcoma specimens. Furthermore, we analyzed CDK7 expression in osteosarcoma cell lines and tissues by Western blot. CDK7-specific siRNA and a highly-selective CDK7 inhibitor, BS-181, were applied to determine the function of CDK7 on osteosarcoma cell growth and proliferation. In addition, the effect of CDK7 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic CDK7 effects in an in vivo environment. Results: Our results demonstrate that higher CDK7 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. Therapeutically, we show that CDK7 knockdown with siRNA or selective inhibition with BS-181 decreases proliferation and induces apoptosis of osteosarcoma cells. Conclusion: This study supports CDK7 overexpression as an independent predictor of poor prognosis and promising therapeutic target for osteosarcoma.

Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review

“…The full search is illustrated in the PRISMA flowchart ( Figure 2 ) . Finally, 70 studies fulfilling the inclusion/exclusion criteria were included in this review [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 6...…”

Scaffold-mediated switching of lymphoma metabolism in culture

“…S2). VitroGel has been previously reported to study various cancer types including pancreatic cancer [58], melanoma [59], breast cancer [60,61], non-small cell lung cancer [62], and osteosarcoma [63]; however, its application in DLBCL investigations is yet to be explored. Though this relatively simple, feasible, and reproducible 3D model led to a more clinically relevant phenotype of DLBCL cells, it lacks the interaction of cancer cells with other cell types comprising tumor microenvironment, such as stromal cells and immune cells.…”

CDK7 in breast cancer: mechanisms of action and therapeutic potential

“…Analyzing breast cancer TMAs for CDK7 (n = 945), the study found that patients with high-grade and extensive tumors, or those with recurrent disease, exhibited lower CDK7 expression. Elevated CDK7 levels were instead associated Breast cancer [70], Gastric cancer [54], Osteosarcoma [115], Synovial sarcoma [116], Thyroid carcinoma [117], T cell acute lymphoblastic leukemia [118] No [95], Head and neck squamous cell carcinoma [121], Thyroid cancer [122], Neuroblastoma [123], Glioblastoma [124], Gastrointestinal stromal tumours [125], Pancreatic cancer [126], Hepatocellular carcinoma [127], Gallbladder cancer [39], Cholangiocarcinoma [128], Colorectal cancer [40], Nasopharyngeal carcinoma [129], Prostate cancer [130], Renal cell carcinoma [131], Urothelial carcinoma [132], Bladder cancer [133], Melanoma [134], Osteosarcoma [135], lymphomas [62], Leukemia [43] No with extended BCSS and prolonged time to distant metastasis [67]. This landscape of disparate findings illustrates the complexity of CDK7's role within breast cancer prognosis and highlights the necessity for further refined and targeted investigations.…”