CDK13-Mediated Cell Cycle Disorder Promotes Tumorigenesis of High HMGA2 Expression Gastric Cancer

Abstract

The inhibitor of CDK4/6 has been clinically used for treating certain types of cancer which are characterized by G0/G1 acceleration induced by the CDK4/6-RB1 pathway. On the contrary, the cell cycle–related molecules are abnormal in over 50% of the patients with gastric cancer (GC), but the efficiency of inhibiting CDK4/6 does not work well as it is expected. In our study, we found HMGA2 promotes GC through accelerating the S–G2/M phase transition, instead of G0/G1. We also found CDK13 is the direct target gene of HMGA2. Importantly, we analyzed 200 pairs of GC and the adjacent tissue and proved the positive relation between HMGA2 and CDK13; moreover, high expression of both genes predicts a poorer prognosis than the expression of single gene does. We explored the effect of the novel CDK12/13 inhibiting agent, SR-4835, on high HMGA2 expression GC and found inhibition of both genes jointly could reach a satisfied result. Therefore, we suggest that inhibition of CDK13 and HMGA2 simultaneously could be an effective strategy for high HMGA2 expression GC. To detect the expression of both genes simultaneously and individually could be of benefit to predict prognosis for GC.

LncRNA SNHG1 promotes renal cell carcinoma progression through regulation of HMGA2 via sponging miR‐103a

“…18 Growing evidence suggested that HMGA2 may be associated with tumorigenesis in a variety of cancers, including lung, breast, kidney and gastric cancers. 8,9,11,19 In our present study, we identified HMGA2 as a down-stream target of miR-103a, and our data revealed that miR-103a directly regulate the expression of HMGA2. These data suggested that SNHG1 promoted RCC proliferation through upregulated HMGA2 by sponging miR-103a.…”

“…HMGA2, a member of high mobility group AT‐hook family, is characterized as an oncofetal protein which is hardly expressed in the differentiated tissues, whereas is highly expressed in a variety of tumors 18 . Growing evidence suggested that HMGA2 may be associated with tumorigenesis in a variety of cancers, including lung, breast, kidney and gastric cancers 8 , 9 , 11 , 19 . In our present study, we identified HMGA2 as a down‐stream target of miR‐103a, and our data revealed that miR‐103a directly regulate the expression of HMGA2.…”

Case Report: Hemophagocytic Lymphohistiocytosis Prior to the Onset of Leukemia in a Boy With CDK13-Related Disorder

“…Interestingly, several recent studies have described the connection of CDK13 influencing cancer development, such as, ovarian cancer, prostate cancer, gastric cancers, hepatocellular carcinoma, etc. ( Dong et al, 2018 ; Greenleaf, 2019 ; Qi et al, 2021 ; Tadesse et al, 2021 ; Wu et al, 2021 ). However, the role of CDK13 in transcription remains poorly understood.…”

Effects of HMGA2 gene silencing on cell cycle and apoptosis in the metastatic renal carcinoma cell line ACHN

“…As a structural transcription factor, HMGA2 can regulate the transcription and activation of a large number of genes, especially those associated with cell cycle and apoptosis. 18 , 19 …”

“…As a structural transcription factor, HMGA2 can regulate the transcription and activation of a large number of genes, especially those associated with cell cycle and apoptosis. 18,19 Cyclin D1 and CDK6 are key proteins that regulate the progression of the cell cycle and they interact to form the cyclin D1-CDK6 complex, which affects the transformation of cells from G1 phase to S phase. 20,21 Transcription factor E2F1 is an important factor involved in cell cycle regulation.…”