CCNA2 expression

Panc1 cells lacking CCN1 showed reduced differentiation and decreased sensitivity to gemcitabine, primarily due to lower expression of genes involved in gemcitabine transport and metabolism. Additionally, we observed that stimulation with TGF-β1 and lysophosphatidic acid increased CCN1 expression in Panc1 cells and induced a shift in mPSCs towards a more myofibroblastic CAF-like phenotype.

Mechanistically, CCNA2 binding to CDK2 phosphorylates the AXIN1 complex, which in turn induces ubiquitination-dependent degradation of β-catenin and inhibits the WNT signaling pathway, thereby failing AT2 cell maintenance. These results uncover smoking-induced CCNA2 overexpression and subsequent WNT/β-catenin signaling inactivation as a hitherto uncharacterized mechanism controlling AT2 cell differentiation and LUAD tumorigenesis.

CCNA2 was up-regulated and mainly located in T cells and B cells in UCEC. Overexpression of CCNA2 predicted unfavorable prognosis of UCEC.

As drug resistance is linked to matrix deposition and neo-angiogenesis, these data suggest that CCN1, due to its multifaceted role, may represent a novel therapeutic target for drug-resistant melanoma. Our data further emphasize the essential role that cancer-associated, (universal) Col1A2-Cre-fibroblasts and extracellular matrix remodeling play in coordinating behavior among different cell types within the tumor microenvironment.

Low CCNA2 expression is significantly associated with worse OS. Thus, CCNA2 might serve as potential biomarker in muscle-invasive UTUC and may be used to characterize a subset of patients having an unfavorable outcome and for future risk-assessment scores.

KLF14 also activated the JNK pathway to induce S-phase arrest and promote the expression of CDK2 and CCNA2. In summary, KLF14 activates the JNK-signaling pathway to induce S-phase arrest in cervical cancer cells.

Halting of cells at S-phase causes induction of apoptosis in cancer cells. Cancer cells exhibiting DNA fragmentation, changes in expression of several apoptotic proteins such as Bcl2, cytochrome-c and formation of cleaved products of caspase 3 and PARP-1 suggests ellagic acid induces cell death via mitochondrial pathway of apoptosis.

Mechanistically, geniposide activated the 5'-AMP-activated protein kinase signaling pathway and inhibited the JNK signaling pathway in SCC-9 cells (western blot analysis). The present results indicated that geniposide is able to inhibit the proliferation and migration of the tongue squamous carcinoma cell line SCC-9, suggesting a potential strategy for OSCC treatment.

Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.

Lastly, MBOAT2 overexpression reduced the infiltration level of CD8 T-cells, plasmacytoid dendritic cells, and activated dendritic cells but triggered a high type-2 T helper/type-1 T helper cell ration (Th2/Th1 ration) in PC. Our findings suggest that MBOAT2 is a potential protooncogene in PDAC that predicts a poor prognosis and is related to KRAS activation and inferior infiltration of CD8 T-cells in PC.

The results of this study suggest that CCN proteins may play roles in LPA- and S1P-induced signaling in prostate cancer cells and are thus potential therapeutic targets.

Furthermore, CCNA2 is positively associated with expressions of immune checkpoints (CD274, CTLA4, HAVCR2, LAG3, PDCD1, and TIGIT) in most cancer types. Our first CCNA2 pan-cancer study contributes to understanding the prognostic and immunological roles and potential upstream molecular mechanisms of CCNA2 in different cancers.

In addition, PKMYT1 was demonstrated to bind to CCNA2, and knocking down PKMYT1 resulted in inhibitory effects on cell proliferation, colony formation ability, migration, invasion and EMT by downregulating CCNA2 expression. PKMYT1 was observed to regulate the proliferation, migration and EMT of OSCC cells by targeting CCNA2, which may be used in the future to improve OSCC treatment.

Furthermore, CDCA7 was found to directly bind to CCNA2, thus promoting its expression. Our results reveal a novel mechanism of CDCA7 that it may act as an oncogene by directly upregulating CCNA2 to facilitate tumor progression in ESCC.

The oncogenic lncRNA HERH-1/4 promoted CCNA2 expression at the transcriptional and post-transcriptional levels and accelerated cell cycle progression in HCC cells. The HERH-1-CREB1-CCNA2 and HERH-4-miR-29b/c-CCNA2 axes served as molecular stimuli for HCC advance.

Furthermore, we found that CCN1 boosted ADAM17-mediated cleavage of TNF receptors through ITGA11 and the soluble decoy receptors generated by this action neutralized TNF activity. Taken together, CCN1 and TNF antagonize each other in esophageal cancer cells.

Our data indicate that E2F1 promotes TNBC proliferation and invasion by upregulating CCNA2 expression. E2F1 and CCNA2 are potential candidates that may be targeted for effective TNBC treatment.

Taken together, our study provided evidence concerning the altered expression of genes in ovarian cancer tissues compared with normal tissues. In vivo and in vitro experiments are required to verify the results of the present study.

Transcriptome datasets of metastatic breast cancer obtained from Oncomine allow the identification of metastatic breast cancer-specific biological functions, pathways, and novel biomarkers to predict clinical outcomes of breast cancer patients. Further functional studies are needed to warrant validation of their roles as functional tumor-promoting or tumor-suppressing genes.

Immunohistochemistry results showed that CCNA2 expression in carcinoma tissues was elevated compared with normal control. CCNA2 identified as a potential immune therapy marker in breast cancer, which were first reported here and deserved further research.

Integrating these molecular aberrations generated a molecular biomarker panel with significant prognostic discrimination (P = 5.8×10-7); adjusting for age, histology, grade, myometrial invasion, TP53 status, and stage, only CCNA2-H/E2F1-H (P = .0003), FBXW7-mu/PPP2R1A-mu (P = .0002), and stage (P = .017) were significant. The generated prognostic molecular classification system identifies dissimilar signaling aberrations potentially amenable to targetable therapeutic options.

A meta-analysis of 11 transcriptome datasets comprising 2,239 primary CRC tumors displayed different CCNA2 (the mRNA coding for cyclin A2) expression levels among the CRC tumor subtypes with highest in CMS1 and lowest in CMS4. Moreover, high expression of CCNA2 was found to be a new independent prognosis factor for CRC tumors.

The results of this study suggest that CDK1 and CCNA2 may be potential therapeutic targets and prognostic biomarkers in patients with PAAD.

Lastly, xenograft experiments indicated that CSN1 promoted HCC tumor growth in vivo. The present study suggested that CSN1 inhibition could represent a potential approach for the prevention of HCC progression and metastasis.

Additionally, the IL-8 mediated MDM2 and CCNA2 expression were affected by NRP-1 knockdown. Our findings suggested that NRP-1 was up-regulated by CAF-secreted IL-8, which subsequently promoted GBC cell proliferation, and these molecules may serve as useful prognostic biomarkers and therapeutic targets for GBC.

This study demonstrates that URB1 contributes to oncogenesis and CRC growth through XBP1-medaited transcriptional activation of ATF4. Therefore, URB1 may be a potential therapeutic target for CRC.

Treatment of NSCLC with LukS-PV combined with p38 and ERK inhibitors reversed the pro-apoptotic and pro-cell cycle arrest effects of LukS-PV. Overall, these findings indicate that LukS-PV has anti-tumor effects in NSCLC and may contribute to the development of anti-cancer agents.

In addition, hsa_circ_0003732 could elevate CCNA2 expression via miR-545, resulting in the promotion of OS cells proliferation. Altogether, our findings demonstrate that hsa_circ_0003732 promotes OS cells proliferation via miR-545/CCNA2 axis and imply hsa_circ_0003732 may be a potential prognosis biomarker and therapeutic target for OS.