Knockdown of KRAB domain-associated protein 1 suppresses the proliferation, migration and invasion of thyroid cancer cells by regulating P68/DEAD box protein 5

Abstract

KRAB domain-associated protein 1 (KAP-1) has been reported to be an oncogene in diverse tumors. KAP-1 was found to have abundant existence in malignant thyroid tissues, but its role in thyroid cancer hasn’t been elucidated clearly. This study was carried out to explore the role of KAP-1 in thyroid cancer, and to clarify its molecular mechanism. The expressions of KAP-1 and P68/DEAD box protein 5 (DDX5) were assessed under the help of qRT-PCR and western blot. Then, we downregulated KAP-1 or upregulated DDX5 by cell transfection in TPC-1 cells. A series of cellular experiments on proliferation, apoptosis, migration and invasion were conducted with CCK-8, EdU, TUNEL, wound-healing and Transwell assays. Besides, the relationship between KAP-1 and DDX5 was verified by co-immunoprecipitation (Co-IP). The results showed that both of KAP-1 and DDX5 were upregulated in thyroid cancer cells. Loss-of-function experiments revealed that KAP-1 knockdown imparted suppressive effects on cell proliferation, migration and invasion, but promoted cell apoptosis. Additionally, KAP-1 was demonstrated to interact with DDX5 and positively regulate DDX5 expression. The following rescued experiments exhibited that the inhibitory effects of KAP-1 knockdown on cellular activities of thyroid cancer and Wnt/β-catenin signaling were also partly reversed by DDX5 overexpression. Moreover, activation of Wnt/β-catenin signaling retarded the anti-tumor activity of KAP-1 knockdown. In conclusion, the data in this study disclosed that KAP-1 silence helped to repress the cell proliferation, migration and invasion by degrading DDK5, so as to hinder the development of thyroid cancer.

The role of tripartite motif-containing 28 in cancer progression and its therapeutic potentials

“…Silencing of TRIM28 inhibits the migration, invasion and EMT process of OC cells via blocking Wnt/β-catenin signaling pathway ( 53 ). Moreover, in thyroid cancer, knockdown of TRIM28 inhibits P68/DEAD box protein 5(DDX5)-mediated Wnt/β-catenin signaling pathway ( 54 ) ( Figure 5 ). In cervical cancer, ZBRK1 can inhibit the transcription of TRIM28, thereby regulating the expression of metastasis-related genes ( 16 ).…”

Microplastics are present in women’s and cows’ follicular fluid and polystyrene microplastics compromise bovine oocyte functionin vitro

“…Proteins known to induce apoptosis, such as BCLAF1 (Kasof et al, 1999), TPM1 (Tang et al, 2018) and AK2 (Lee et al, 2007) were up-regulated in MPs incubated oocytes, while the MVP (Sutovsky, 2009), a known oocyte protector, was down-regulated. Additionally, DDX5 (Lan et al, 2022) was up-regulated and HSP90AA1 (Liu et al, 2018) was down-regulated in the presence of MPs. Together with an up-regulation of HNRNPM (Chen et al, 2017; Kogasaka et al, 2013) and TBCA (Nolasco et al, 2005), and down-regulation of PADI6 (Kan et al, 2011; Yurttas et al, 2008), these differentially abundant proteins can provide a mechanistic explanation as to the reduced maturation rate observed in oocytes exposed to MPs, since these proteins are important for nuclear maturation, spindle formation and microtubule and organelle organization (summarized in Fig.…”

Ubiquitin-modifying enzymes in thyroid cancer：Mechanisms and functions

“…Lan et al discovered that the expression of E3 ligase KRAB-associated protein 1 (KAP-1) is upregulated in thyroid cancer cells. It positively regulates dead-box helicase 5 ( DDX5 ) expression in PTC cells by interacting with DDX5, which, in turn, upregulates β-catenin expression and activates the signaling pathway [ 87 ].…”