TL;DR
It is indicated that chrysin treatment is associated with selective cytotoxicity and concurrent modulation of HPV16 E6 protein levels and several cancer-related miRNAs in CaSki cells.
Cervical cancer (CC) remains a major cause of cancer-related mortality among women worldwide, primarily driven by persistent infection with high-risk human papillomavirus (HPV) types. Given that natural products with selective antitumour properties offer potential for novel therapies, we evaluated the cytotoxic, antiproliferative, and molecular effects of cinnamon essential oil (CEO) on HPV-positive cervical cancer cell lines (HeLa and SiHa) and nontumorigenic keratinocytes (HaCaT). Cells were exposed to a range of dilutions of CEO. Cell viability was determined by WST-1 and sulforhodamine B assays. Apoptosis was assessed using Annexin V/PI staining, caspase-3/8/9 activation, and mitochondrial membrane potential (Δψm) loss by flow cytometry. Proliferation was measured using EdU incorporation, and senescence was measured by β-galactosidase activity. Genome-wide transcriptional changes and HPV E6/E7 oncogene expression were analysed by RNA-Seq and validated with qPCR. CEO induced dose-dependent cytotoxicity and inhibited proliferation in cervical cancer cells, while HaCaT cells were significantly more resistant. Apoptosis was evidenced by Annexin V/PI positivity, activation of caspases -8, -9, and -3, and significant loss of mitochondrial membrane potential. No significant senescence induction was observed. Additionally, CEO also significantly downregulated HPV E6 / E7 oncogene expression in HeLa and SiHa cells. Transcriptomic analysis revealed broad differential gene expression, including upregulation of stress and apoptosis-related genes and downregulation of proliferation, oxidative phosphorylation, and viral-related pathways. CEO exerts selective cytotoxic and antiproliferative effects on cervical cancer cells by triggering mitochondria-mediated apoptosis and suppressing HPV oncogenes. These findings support CEO as a potential source of bioactive compounds for complementary strategies against HPV-related malignancies.
Despite being preventable, cervical malignancy remains a major cause of mortality among women,particularly in low-resource settings with limited screening availability. Although high-risk humanpapillomavirus (HPV) types 16 and 18 are the primary causative agents, malignant progressionoccurs in only a minority of cases, suggesting that viral presence must be supplemented by host-specific molecular, genetic, and epigenetic factors. Thus, cervical carcinogenesis is a complex multistep biological process. Recent research has identified microRNAs (miRNAs) as prominent regulators of this process, playing key roles in post-transcriptional gene modulation. These small non-coding RNA molecules govern essential functions, including cellular proliferation, apoptosis, cell cycle regulation, epithelial-mesenchymal transition (EMT), DNA damage response, and immune evasion. By binding to the 3' untranslated regions (3′-UTRs) of target mRNAs, miRNAs maintain cellular homeostasis through mRNA degradation and translational inhibition. The current literature confirms significant miRNA dysregulation in cervical cancer; a phenomenon closely linked to HPV E6 and E7 oncoproteins. While targeting tumor suppressors such as p53 and retinoblastoma protein (pRb), these viral oncoproteins simultaneously manipulate specific miRNAs, oncomiRs, or tumor-suppressive miRNAs to exacerbate malignant transformation. Notably, the dysregulation of certain miRNAs significantly impacts tumor invasion, angiogenesis, metastatic potential, and chemoradiotherapy resistance. Consequently, this study details the molecular pathways contributing to malignancy through altered miRNA expression during HPV infection and evaluates their clinical potential as non-invasive diagnostic tools, prognostic indicators, and innovative therapeutic targets for HPV-associated cancers.
Cervical cancer is a leading cause of female malignancy worldwide. While microRNA-4327 (miR-4327) has been implicated as a potential oncogene, its functional role and molecular mechanisms in cervical cancer pathogenesis remain unclear. This study aimed to determine the oncogenic function of miR-4327 and elucidate its downstream regulatory mechanism in cervical cancer pathogenesis. We measured miR-4327 expression in clinical cervical cancer tissues and cell lines using quantitative real-time PCR (qRT-PCR). We then assessed its effects on proliferation, migration, invasion, and cell cycle progression through functional assays including cell counting kit-8 (CCK-8), colony formation, transwell, and flow cytometry. To evaluate tumor growth in vivo, we established a xenograft model in non-obese diabetic (NOD)-severe combined immune-deficient (scid) mice. Using bioinformatic analysis and luciferase reporter assays, we identified TP53 as a direct target of miR-4327 and further validated this regulatory relationship with gain- and loss-of-function experiments. We found that miR-4327 was significantly upregulated in cervical cancer and promoted malignant phenotypes such as proliferation, migration, invasion, and cell cycle progression in vitro. Consistent with this, overexpression of miR-4327 accelerated tumor growth in vivo. Mechanistically, we confirmed TP53 as a direct functional target of miR-4327. Knocking down TP53 phenocopied the oncogenic effects of miR-4327, while restoring TP53 expression rescued the tumor-promoting effects mediated by miR-4327. These findings reveal a novel miR-4327/TP53 regulatory axis and nominate miR-4327 as a potential therapeutic target for intervention.
Background: Human Papillomavirus (HPV) type 16 is one of the most common sexually transmitted viruses, suggesting a potential long-standing link to prostate cancer. The viral genome has been seen as most demonstrated effect to prostate carcinogenesis and levels of miRNA-330 expression, ignoring the capability of miRNA-330 in tumor-suppression role by regulating cell death and proliferation pathways, Human Papillomavirus type 16 kept the tumor activity. This inapparent functional reversal or equal could lead to different results depending on the potency of the virus to produce the oncogenic proteins, Because of the unknown influence of these factors, given the limited number of studies linking these two factors. Objective: the aim of this study is to find the relationship between the Human Papillomavirus type 16 infection and develop of the prostate cancer in the sphere of influence of the microRNA-330. Methods: the study has conducted in a cohort of prostate cancer patients after the samples were isolated from the Hospital of the (Middle Euphrates Cancer Center), ranging from 47 to 98 years old (n = 100), and divided into two group (PCa with HPV16 and PCa without HPV16). quantified the levels of viral genome and miRNA-330 were done by RT-qPCR. Results: The results showed a positive correlation, with a P-value < 0.05, indicating a clear correlational effect of latent human Papillomavirus type 16 infection. This correlation was further supported by the high gene expression rate of miRNA-330 about 5.27 ± (1.3) in PCa patients with HPV16, while 1 ± (0.22) in PCa patients without HPV16. Conclusions: This study provides novel insights into the nature and progression of prostate tumors and the role of miRNA-330 as a biomarker. The study took place in Najaf, Iraq.
As the incidence of Breast cancer continues to rise globally, understanding the molecular mechanisms by which probiotics can influence cancer cell behavior is crucial. Thisresearch explores the gene regulatory mechanism ofpotential anti-cancer properties of cell-free supernatants derived from Bifidobacterium bifidum and Lactobacillus acidophilus on Breast cancer cell lines, including MCF-7 and MDA-MB-231. We utilized a variety of experimental techniques, including MTT assays, BrdU, flow cytometry, evaluation of caspase activity and BAX/BCL-2 ratio, RT-PCR, Western blot analysis, and mimic miRNA transfection, to evaluate apoptosis induction and uncover the involved gene regulatory mechanisms throughout miRNAs. After exposing the cells with probiotic supernatants for 48 h at concentrations between 0.5 and 40 µg/mL, we observed a significant induction of apoptosis in both cell lines. Our investigation centered on four oncomiRs: miR-21-5p, miR-155-5p, miR-150-5p, and miR-223-3p, revealing notable changes in the levels of miR-155-5p and miR-21-5p. Further analysis indicated that the supernatants increased the expression of their target genes and proteins, PDCD4 and PTEN, which are essential for regulating apoptosis as tumor suppressor factors. we confirmed this gene regulatory properties by transfection of mimic miR-21-5p and miR-155-5p, the anticipated increase in PDCD4 and PTENwas less pronounced in transfected cells. This finding suggests that probiotics can effectively downregulate certain oncomiRs and enhance their target tumor suppressor genes and protein levels. the down-regulation of oncomiRs may display positive effects of probiotics, leading to inhibition of tumor growth and anti-proliferative outcomes. Our results emphasize the intricate relationships among probiotics, miRNAs, and tumor suppressor proteins, highlighting their potential significance in cancer treatment. This study calls for further exploration of these interactions to develop improved therapeutic strategies for Breast cancer through the modulation of cellular pathways by probiotics.
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