STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway

Zhang, Chengfei; Wang, Xiaoming; Fang, Dan; Xu, Ping; Xiao, Mingzhong; Hu, Chao; Abdelatty, Alaa; Wang, Mei; Xu, Haojun; Sun, Qi; Zhou, Guoren; She, Junjun; Xia, Jinglin; Hui, Kam M.; Xia, Hongping

doi:10.7150/thno.48112

Cited by 32 publications

(27 citation statements)

References 58 publications

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“…Based on the results of bioinformatics analysis and molecular docking, we also found that aurora kinase A (AURKA) and Polo-like kinase 1 (PLK1) may also be the key proteins regulating TSA anti-LUAD. PLK1 is known to play an important role in initiating, completing, and maintaining the cell mitotic cycle 25 . Elevated levels of PLK1 transcription, or protein expression, have been found in a variety of human solid tumors, including lung, breast, stomach, cervical, and colon cancers 26 .…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway

Zhang

Zhou

et al. 2021

Sci Rep

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Lung adenocarcinoma (LUAD) belongs to a subgroup of non-small cell lung cancer (NSCLC) with an increasing incidence all over the world. Tanshinone IIA (TSA), an active compound of Salvia miltiorrhiza Bunge., has been found to have anti-tumor effects on many tumors, but its anti-LUAD effect and its mechanism have not been reported yet. In this study, bio-information analysis was applied to characterize the potential mechanism of TSA on LUA, biological experiments were used to verify the mechanisms involved. TCGA, Pubchem, SwissTargetPrediction, Venny2.1.0, STRING, DAVID, Cytoscape 3.7.2, Omicshare, GEPIA, RSCBPDB, Chem Draw, AutoDockTools, and PyMOL were utilized for analysis in the bio-information analysis and network pharmacology. Our experiments in vitro focused on the anti-LUAD effects and mechanisms of TSA on LUAD cells (A549 and NCI-H1975 cells) via MTT, plate cloning, Annexin V-FITC and PI dual staining, flow cytometry, and western blot assays. A total of 64 differentially expressed genes (DEGs) of TSA for treatment of LUAD were screened out. Gene ontology and pathway analysis revealed characteristic of the DEGs network. After GEPIA-based DEGs confirmation, 46 genes were considered having significant differences. Further, 10 key DEGs (BTK, HSD11B1, ADAM33, TNNC1, THRA, CCNA2, AURKA, MIF, PLK1, and SORD) were identified as the most likely relevant genes from overall survival analysis. Molecular Docking results showed that CCNA2, CDK2 and PLK1 had the lowest docking energy. MTT and plate cloning assays results showed that TSA inhibited the proliferation of LUAD cells in a concentration-dependent manner. Annexin V-FITC and PI dual staining and flow cytometry assays results told that TSA promoted the apoptosis of the two LUAD cells in different degrees, and induced cycle arrest in the G1/S phase. Western blot results showed that TSA significantly down-regulated the expression of CCNA2, CDK2, AURKA, PLK1, and p-ERK. In summary, TSA could suppress the progression of LUAD by inducing cell apoptosis and arresting cell cycle, and these were done by regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway. These findings are the first to demonstrate the molecular mechanism of TSA in treatment of LUAD combination of network bio-information analysis and biological experiments in vitro.

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Section: Discussionmentioning

confidence: 99%

Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway

Zhang

Zhou

et al. 2021

Sci Rep

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“…Nevertheless, the miRNAs function often rely on the target downward protein [ 28 ]. Serine/Threonine Kinase 39 (STK39) encodes a serine/threonine kinase affecting cellular stress response pathway [ 34 ]. This kinase is closest implicated in oncogenesis, such as HCC, osteosarcoma and so on [ 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of long non-coding RNA CDKN2B-AS1 suppresses the progression of breast cancer by miR-122-5p/STK39 axis

Qin

Ning

et al. 2021

Bioengineered

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The lncRNAs have been made certain to take part in the development of most cancers in multiple ways. Here, our purpose is to making observation of the biological role and function of lncRNA CDKN2B-AS1 in human breast cancer. Twenty-eight pairs of breast cancer tissue and adjacent normal tissue from breast cancer patients were used to investigate the expression of CDKN2B-AS1 by qRT-PCR. And a lentivirus-shRNA guided CDKN2B-AS1 were to reduce its expression. The function of CDKN2B-AS1 was analyzed using a series of in vitro assays. Meanwhile, the xenograft model was used to further explicate the role of CDKN2B-AS1 in breast cancer. As for the results, there is a relative rich expression of CDKN2B-AS1 in breast cancer tissues compared with the corresponding adjacent normal tissues. Compared with the human breast epithelial cell line, the abundant expression of CDKN2B-AS1 in breast cancer cells were revealed as well. Then, knockdown CDKN2B-AS1 inhibited the malignant biological behaviors of MCF7 and T47D cells. In mechanism, CDKN2B-AS1 sponged the miR-122-5p to regulate STK39 expression. Furthermore, the inhibition effect with sh-CDKN2B-AS1 on breast cancer cells was alleviated by miR-122-5p inhibitor. Last, an in vivo model also confirmed that knockdown CDKN2B-AS1 retarded the growth of breast cancer. Our data concluded that knockdown of CDKN2B-AS1 suppresses the progression of breast cancer by miR-122-5p/STK39 axis.

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“…In recent years, the molecular mechanism of STK39 in the tumorigenicity and tumor progression of several cancer types has been studied, including HCC ( Zhang et al., 2021 ). However, the genetic characteristics and molecular mechanisms of STK39 in CCA are still remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal expression of STK39 has been correlated with various human diseases, such as hypertension ( Wang et al., 2009 ), stroke ( Josiah et al., 2021 ), and type I diabetes ( Forgetta et al., 2020 ). In addition, many studies have pointed out that STK39 acts as an important regulator in the occurrence and progression of malignancies ( Li et al., 2016 ; Huang et al., 2017 ; Yang et al., 2018 ), including hepatocellular carcinoma (HCC) ( Zhang et al., 2021 ). However, limited research has explored the molecular mechanism of STK39 in CCA.…”

Section: Introductionmentioning

confidence: 99%

STK39 enhances the progression of Cholangiocarcinoma via PI3K/AKT pathway

Hao¹,

Zhang²,

Lu³

et al. 2021

iScience

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Highlights STK39 was overexpressed in CCA, negatively associated with the prognosis of patients with CCA STK39 knockdown suppressed cell proliferation and invasion. STK39 overexpression facilitated tumor aggressiveness STK39 mediates oncogenic effects on CCA cells by activating the PI3K/AKT signaling pathway STK39 reduces CCA sensitivity to gemcitabine. Increased expression of STK39 may be mediated by dysregulation of miR-26a-5p

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STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway

Cited by 32 publications

References 58 publications

Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway

Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway

Knockdown of long non-coding RNA CDKN2B-AS1 suppresses the progression of breast cancer by miR-122-5p/STK39 axis

STK39 enhances the progression of Cholangiocarcinoma via PI3K/AKT pathway

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