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Hindi Perspective, Cocr Vol: 7 Issue: 8
The Role of NEK6 in Ovarian Cancer: Expression Profiles, Prognostic Implications, and Functional Insights
J. K. Rowling*
Department of Oncology, Sir Anthony Mamo Oncology Centre, Imsida, Malta
*Corresponding Author: J. K. Rowling
Department of Oncology, Sir Anthony Mamo Oncology Centre, Imsida, Malta,
E-mail: rowling.janiee65@gmail.com
Received: August 05, 2024; Manuscript No: COCR-24-158568
Editor Assigned: August 11, 2024; PreQC Id: COCR-24-158568 (PQ)
Reviewed: August 18, 2024; QC No: COCR-24-158568 (Q)
Revised: August 25, 2024; Manuscript No: COCR-24- 158568 (R)
Published: August 29, 2024; DOI: 10.4173/cocr.7(8).368
Citation: J. K. Rowling. (2024) The Role of NEK6 in Ovarian Cancer: Expression Profiles, Prognostic Implications, and Functional Insights. Clin Oncol Case Rep 7:8
Abstract
Ovarian Cancer (OC) is a leading malignancy among female reproductive tumors, often associated with late diagnosis and poor prognosis. Recent studies have implicated the novel serine/threonine kinase NEK6 as a critical player in cancer progression, but its role in OC remains unclear. This study investigates the expression of NEK6 in OC tissues and its impact on the disease’s progression and patient prognosis. Bioinformatics analyses demonstrated elevated NEK6 expression across multiple cancers, including OC. Immunohistochemical (IHC) staining revealed that NEK6 expression was significantly higher in OC tissues compared to normal ovarian tissues and was associated with clinicopathological factors such as histological grade and metastasis. Functional assays, including MTT, Transwell, and flow cytometry, showed that NEK6 silencing via siRNAs suppressed OC cell growth, migration, and invasion while promoting apoptosis. Kaplan?Meier survival analysis highlighted a correlation between high NEK6 expression and reduced overall survival in OC patients. These findings suggest that NEK6 plays a critical role in OC progression and could serve as a potential biomarker and therapeutic target.
Keywords: Ovarian cancer; NEK6; Bioinformatics analysis, Immunohistochemistry; Prognosis;
Introduction
Ovarian Cancer (OC) is the fifth most common cause of cancer-related deaths among women worldwide and is characterized by its asymptomatic progression and poor survival rates. Despite advances in early detection and therapeutic strategies, OC remains challenging to treat, necessitating the identification of novel biomarkers and therapeutic targets. The serine/threonine kinase NEK6 has emerged as a candidate, known for its involvement in cell cycle regulation, mitotic progression, and tumorigenesis in various cancers. However, its role in OC is not well understood. This study aims to elucidate the expression, function, and clinical significance of NEK6 in OC..
Methods
Bioinformatics analysis: NEK6 expression profiles across cancers, including OC, were analyzed using public databases such as. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).
Immunohistochemistry (IHC): IHC staining was performed on OC and normal ovarian tissues to evaluate NEK6 expression. The staining intensity was classified into weak, moderate, or strong categories and correlated with clinicopathological factors.
RT-qPCR and western blotting: Quantitative reverse transcription PCR (RT-qPCR) and Western blot analyses were conducted to quantify NEK6 mRNA and protein levels in OC tissues and cell lines.
Cell functional assays
MTT assay: Evaluated cell proliferation after NEK6 knockdown using siRNAs.
Transwell migration and invasion assays: Assessed the impact of NEK6 silencing on OC cell motility and invasive potential. Flow cytometry: Analyzed the effects of NEK6 silencing on apoptosis.
Statistical analysis: The relationship between NEK6 expression and clinicopathological factors was assessed using Chi-square tests, and Kaplanâ??Meier survival analysis was used to evaluate its prognostic significance.
Results
NEK6 expression in OC
Bioinformatics analysis revealed significantly elevated NEK6 expression in OC tissues compared to normal ovarian tissues (p < 0.05). IHC staining showed moderate to strong NEK6 expression in 67.27% of OC tissues, with negative or weak staining in normal ovarian tissues. RT-qPCR and Western blotting confirmed higher NEK6 mRNA and protein levels in OC tissues and cell lines (SK-OV-3 and A2780).
Correlation with clinicopathological factors
High NEK6 expression was significantly associated with advanced histological grades (p= 0.008) and metastasis (p=0.006). Kaplanâ??Meier analysis indicated that patients with high NEK6 expression had significantly poorer overall survival rates compared to those with low expression (p=0.025).
Functional role of Nek6 in OC progression
Cell proliferation: NEK6 silencing via siRNAs inhibited the proliferation of SK-OV-3 and A2780 cells.
Migration and invasion: Transwell assays demonstrated reduced migration and invasion capabilities in NEK6-silenced cells.
Apoptosis: Flow cytometry analysis revealed increased apoptosis in NEK6-silenced cells, highlighting its role in promoting OC cell survival.
Discussion
The findings of this study underscore the critical role of NEK6 in OC progression. Elevated NEK6 expression in OC tissues and its correlation with poor clinicopathological outcomes suggest its potential as a biomarker for OC diagnosis and prognosis. The functional assays demonstrate that NEK6 promotes OC cell growth, migration, and invasion while inhibiting apoptosis, aligning with its established role in other cancers.
Mechanisms of NEK6 in OC
NEK6 may drive OC progression through several mechanisms:
Cell cycle regulation: NEK6 regulates mitotic spindle formation, and its overexpression may result in uncontrolled cell proliferation.
Activation of signaling pathways: NEK6 influences oncogenic signaling pathways, including PI3K/AKT and MAPK, which are critical for cancer cell survival and metastasis.
Evasion of apoptosis: NEK6 may inhibit pro-apoptotic pathways, enhancing OC cell resistance to therapy
Therapeutic Implications
Targeting NEK6: Developing small-molecule inhibitors or RNAbased therapies targeting NEK6 could offer a novel approach to OC treatment.
Combination therapies: Combining NEK6 inhibitors with chemotherapy or immunotherapy may enhance treatment efficacy and overcome drug resistance.
Biomarker potential: Incorporating NEK6 expression analysis into clinical workflows could refine patient stratification and inform personalized treatment strategies.
Future Directions
Preclinical studies: Further studies using animal models are needed to validate the therapeutic potential of NEK6 inhibition in OC.
Exploration of mechanisms: Detailed investigations into the molecular mechanisms linking NEK6 to OC progression could uncover additional therapeutic targets.
Clinical trials: Translating these findings into clinical trials will be crucial for assessing the safety and efficacy of NEK6-targeted therapies.
Conclusion
This study highlights NEK6 as a key contributor to OC progression, with elevated expression linked to poor prognosis and aggressive tumor behavior. The findings provide a foundation for future research into NEK6 as a diagnostic biomarker and therapeutic target, offering hope for improved outcomes in OC management. Addressing the challenges of late diagnosis and treatment resistance in OC requires innovative approaches, and targeting NEK6 represents a promising avenue in this endeavor.
