Identification of HIPK3 as a potential biomarker and an inhibitor of clear cell renal cell carcinoma

Abstract

Invasion and metastasis are the main causes of poor prognosis in patients with clear cell renal cell carcinoma (ccRCC). The homeodomain interacting protein kinases (HIPKs) can regulate cell proliferation and apoptosis. Little is known about the prognostic role of HIPKs in ccRCC. Here we use Kaplan-Meier survival analysis and multivariate analysis to analyze the correlation of overall survival (OS) and disease–free survival (DFS). ROC curves analyzed the relationship between clinicopathological parameters and HIPK3 expression in ccRCC. Univariate analysis and multivariate analysis confirmed that the expression of HIPK3 was associated with OS (HR, 0.701; P=0.041) and DFS (HR, 0.630; P=0.012). Low HIPK3 expression was a poor prognostic factor and HIPK3 expression was significantly down-regulated in ccRCC cancer tissues when compared with normal renal tissues. In vitro cell results also confirmed that HIPK3 over-expression could inhibit tumor growth and malignant characteristics. The results indicate that low expression of HIPK3 in ccRCC tissues is significantly associated with poor survival rates in tumor patients, and HIPK3 may be used as a valuable biomarker and inhibitor of ccRCC.

Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3

“…In comparisons of CCA tissue with normal adjacent cholangiocytes, the intensity of HIPK3 staining was dramatically higher in the latter based on H-scores. A previous study noted that low HIPK3 expression indicated a poor prognosis in clear-cell renal-cell carcinoma tissues 36 . Furthermore, using Chi-square and Fisher's exact tests, as well as univariate and multivariate regression analysis, we discovered a significant correlation between longer patient survival time and high HIPK3 H-scores in CCA patients.…”

“…HIPKs regulate a variety of biological processes in response to various external stimuli, including signal transduction, apoptosis, embryonic development, DNA damage response, and cellular proliferation 32 . HIPK3 is a tumor suppressor in breast 33 , lung 34 , colorectal 35 , and renal cell carcinomas 36 as well as in the advancement of esophageal squamous-cell carcinoma tumors 37 . According to our RT-qPCR and Western blot results, the expression of HIPK3 was negatively and significantly correlated with miR-205-5p activity.…”

The potential of circHIPK3 as a biomarker in chronic myeloid leukemia

“…demonstrated that circHIPK3, by binding with miR-561 and miR-192, activates NLRP3 macrophage inflammation and TLR4 pathway in gouty arthritis ( 32 ). Regarding the oncogenic process, several studies have shown that the regulation exerted by circHIPK3 by binding with multiple miRNAs plays an important role in different types of cancer, such as breast ( 36 ), pancreas ( 37 ), lung ( 38 ), gut ( 39 ), liver ( 40 ), brain ( 41 ), esophagus ( 33 ), renal ( 42 ) and blood ( 43 ). Some of these studies investigated the cellular signaling pathways involved in circHIPK3 action and, predominantly, increased levels of circHIPK3 combined with miRNA binding result in tumor progression ( 27 ).…”

MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 in allergic conjunctivitis

“…As an intracellular serine/threonine protein kinase, HIPK3 negatively regulates cell apoptosis through phosphorylation of Jun and Runx2, and also enhances androgen receptor (AR)-mediated transcriptional activation (20). It has also been reported to accelerate the progression of multiple diseases, such as certain cancers (21,22), Huntington's disease (23), and sepsis (11). Additionally, HIPK3 also could regulate inflammatory cytokines to affect the inflammatory response (11).…”