Key Takeaways & Executive Findings
- •• UCA1 is upregulated in cisplatin-resistant cervical cancer tissues and cells, promoting malignancy via miR-195-5p/IKBKB axis. • UCA1 knockdown inhibits proliferation, migration, invasion, and induces apoptosis in DDP-resistant HeLa cells. • UCA1 silencing suppresses tumor growth in vivo and modulates BNIP3/BNIP3Δex2 and NF-κB pathway. • The UCA1/miR-195-5p/IKBKB axis represents a promising therapeutic target for overcoming cisplatin resistance in cervical cancer.
Abstract
Cisplatin resistance is a major cause of poor prognosis in patients with cervical cancer. Dysregulation of long noncoding RNAs (lncRNAs) plays a key role in chemoresistance. Our results reveal that the lncRNA UCA1 is upregulated in cisplatin (DDP)-resistant cervical cancer tissues and HeLa cells. Mechanistically, the lncRNA UCA1 acts as a sponge for miR-195-5p, targeting IKBKB. UCA1 enhances proliferation, migration, and invasion while reducing apoptosis in DDP-resistant HeLa cells via the miR-195-5p/IKBKB axis. Additionally, UCA1 upregulates BNIP3Δex2 and p-p65 expressions and downregulates BNIP3 expression in DDP-resistant HeLa cells. Abnormal expressions of BNIP3Δex2 and BNIP3 significantly alter the malignant progression of HeLa/DPP cells. In vivo, UCA1 silencing inhibits growth, enhances apoptosis, and upregulates IKBKB, BNIP3Δex2, and p-p65 expressions while downregulating BNIP3 expression in subcutaneous xenografts in nude mice by targeting miR-195-5p. Overall, this study highlights a novel promising target for the treatment of DDP-resistant cervical cancer.
1. Introduction
Cervical cancer is the fourth most common cancer among women worldwide [1], with 604,127 cases and 341,831 deaths in 2020 [2]. Treatment primarily includes surgery, radiotherapy, and chemotherapy [3], with chemotherapy being the main clinical strategy for advanced cervical cancer [4]. Cisplatin (DDP), a commonly used chemotherapeutic agent, induces severe DNA damage and cell death [5]. While effective initially, most patients develop DDP resistance, leading to reduced drug efficacy and potential cancer recurrence or metastasis [6]. The prognosis for patients with recurrent or advanced metastatic cervical cancer remains poor, with a 5-year survival rate of 16.5% [7]. Thus, exploring the mechanism of DDP resistance is crucial for improving chemotherapy outcomes.
Long noncoding RNA (lncRNA) are a novel class of noncoding RNAs longer than 200 nucleotides that do not encode proteins [8]. They play significant roles in cancer processes, such as proliferation, metastasis, and apoptosis [9–11]. LncRNA UCA1 (urogenital carcinoma antigen 1) is highly expressed in multiple tumors, including gastric cancer [12], colorectal cancer [13], and breast cancer [14]. UCA1 has been reported to enhance DDP resistance in various cancers, such as gastric cancer [15], lung adenocarcinoma [16], and ovarian cancer [17]. Recent studies have shown that UCA1 accelerates cervical cancer progression by targeting SMARCD3 or miR-145 [18,19]. Therefore, we hypothesized that UCA1 may enhance DDP resistance in cervical cancer. LncRNAs can act as competitive RNAs of miRNAs (ceRNAs) to regulate tumor metastasis and drug resistance [20,21]. Bioinformatics analysis suggested that miR-195-5p targets and binds to UCA1 and IKBKB. However, it remains unclear whether UCA1 induces DDP resistance in cervical cancer cells via the miR-195-5p/IKBKB axis.
Loading authentic research manuscript (Pages 1–5)...
Bi Wang, Ling Li, Zhengyu Wu, Xuanzhen Qian, Wenfeng Yu, Zhi Huang (2026). Long noncoding RNA UCA1 knockdown inhibits cisplatin-resistant cervical cancer tumorigenesis via the miR-195-5p/IKBKB axis. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2025032
Research & Educational Purpose Only:The translations, structured abstracts, analytical annotations, and data reports provided by SinoBioData are intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoBioData claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What is the role of UCA1 in cisplatin-resistant cervical cancer?
UCA1 is upregulated in cisplatin-resistant cervical cancer tissues and cells, and it promotes tumorigenesis by sponging miR-195-5p to upregulate IKBKB, enhancing proliferation, migration, and invasion while reducing apoptosis.
How does UCA1 knockdown affect cervical cancer cells?
UCA1 knockdown inhibits proliferation, migration, and invasion, and induces apoptosis in DDP-resistant HeLa cells, and suppresses tumor growth in vivo.
What is the molecular mechanism involving miR-195-5p and IKBKB?
UCA1 acts as a ceRNA for miR-195-5p, thereby upregulating IKBKB expression, which activates NF-κB signaling and modulates downstream targets like BNIP3 and BNIP3Δex2.
What are the clinical implications of this study?
The UCA1/miR-195-5p/IKBKB axis provides a novel therapeutic target for overcoming cisplatin resistance in cervical cancer, potentially improving patient outcomes.
What methods were used in this study?
The study used clinical specimens, cell culture, in vivo xenograft models, and molecular biology techniques to assess UCA1 expression, cell behavior, and signaling pathways.
Related Technical Papers & Translations
Adverse Events Reporting System for Vaccine Safety Surveillance: A Comprehensive Analysis
Background: Adverse events following immunization (AEFI) are critical to monitor for vaccine safety. This study evaluates the performance of an adverse events reporting system (AERS) integrated with a vaccine adverse event reporting system (VAERS) to enhance surveillance. Methods: We analyzed data from multiple sources including the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), and the Clinical Immunization Safety Assessment (CISA) network. A novel framework was developed to integrate these systems, incorporating natural language processing for signal detection. Results: The integrated system improved detection of rare adverse events by 25% compared to traditional methods. The system identified new safety signals for influenza and COVID-19 vaccines. Conclusions: The proposed AERS framework enhances vaccine safety surveillance, enabling timely identification of potential risks. Integration of diverse data sources and advanced analytics is essential for robust pharmacovigilance.
Efficacy and Safety of Ferric Carboxymaltose in Treating Iron Deficiency Anemia: A Meta-Analysis of Randomized Controlled Trials
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous ferric carboxymaltose (FCM) has emerged as a promising treatment. This meta-analysis aimed to evaluate the efficacy and safety of FCM compared to other iron therapies or placebo in adults with IDA. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs) comparing FCM with active comparators or placebo in adults with IDA were included. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Pooled estimates were calculated using random-effects models. Results: A total of 15 RCTs involving 4,856 patients were included. FCM significantly increased Hb levels compared to placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.9-1.5) and was non-inferior to other intravenous iron preparations. The risk of AEs was similar between FCM and comparators (risk ratio [RR] 1.05, 95% CI 0.95-1.16), but FCM was associated with a lower risk of gastrointestinal AEs compared to oral iron. Serious adverse events were rare and comparable across groups. Conclusion: Ferric carboxymaltose is effective and safe for treating IDA, offering a convenient single-dose option with a favorable safety profile. These findings support its use in clinical practice.
Adverse Drug Reactions Associated with COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) associated with these vaccines have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and types of ADRs following COVID-19 vaccination. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates, and subgroup analyses were performed by vaccine type and dose. Results: A total of 45 studies with 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4%). Common local reactions included injection site pain (48.2%), swelling (22.5%), and redness (18.7%). Systemic reactions included fatigue (34.6%), headache (28.9%), and myalgia (22.3%). Serious ADRs were rare (0.02%). Subgroup analysis showed higher incidence with mRNA vaccines compared to viral vector vaccines. Conclusion: COVID-19 vaccines are associated with a high incidence of mild-to-moderate ADRs, but serious ADRs are extremely rare. These findings support the overall safety of COVID-19 vaccination programs.