Li Zhou

M5C-driven stabilization of SERPINB5 promotes cervical cancer progression and chemotherapy resistance

Abstract RNA 5-methylcytosine (m 5 C) plays a critical role in cancer, yet its functional mechanisms and therapeutic relevance in cervical cancer remain unclear. Here, we generate the first base-resolution m 5 C transcriptome maps in cervical cancer, revealing globally elevated m 5 C levels in tumors. By integrating spatial transcriptomics and single-cell RNA-seq, we identify SERPINB5 as a novel m 5 C-regulated oncogenic effector. m 5 C modification enhances SERPINB5 mRNA stability and protein expression, promoting tumor growth, metastasis, and resistance to microtubule-targeting chemotherapeutics. Mechanistically, SERPINB5 upregulates mitotic regulators and microtubule motor proteins, including CENPE, enhancing mitotic progression and counteracting drug-induced mitotic arrest. Loss-of-function experiments demonstrate that SERPINB5 depletion sensitizes cervical cancer cells to paclitaxel and vincristine, while its reintroduction restores chemoresistance even in m 5 C-deficient cells. Our study uncovers a previously unrecognized m 5 C–SERPINB5 axis as a central driver of cervical cancer malignancy and chemoresistance, highlighting SERPINB5 as a clinically actionable target to improve outcomes for patients receiving microtubule-targeting chemotherapy.

Oxycodone vs the Combination of Fentanyl and Remifentanil for General Anesthesia in Laparoscopic Uterine Myomas Surgery: A Prospective, Randomized, Controlled Study

This study evaluated whether oxycodone alone could substitute for fentanyl combined with remifentanil for general anesthesia in laparoscopic uterine myoma surgery. 90 adult female patients were randomized into three groups: oxycodone 0.35 mg/kg (Group A), oxycodone 0.30 mg/kg (Group B), or fentanyl 5 μg/kg (Group C) for induction. Anesthesia was maintained with propofol plus saline (Groups A/B) or remifentanil (Group C). Primary outcomes included Numerical Rating Scale (NRS) pain scores in the Post-Anesthesia Care Unit (PACU). Secondary outcomes were intubation reaction, vital signs, extubation/PACU times, Ramsey Sedation Scores (RSS) in PACU, NRS pain scores and adverse events within 48 hours postoperatively. Intubation reactions were rare (one case each in Groups B/C, none in Group A). Group B had significantly lower PACU NRS scores than Group C (0.6 ± 0.7 vs 1.3 ± 1.4, P = 0.011), while Group A showed a nonsignificant trend (0.8 ± 0.9 vs 1.3 ± 1.4, P = 0.051). RSS scores, extubation/PACU times, and 48-hour NRS scores were comparable. However, oxycodone groups had longer postoperative evacuation times than fentanyl group (Group A vs Group C: 20.0 ± 7.3 hours vs 16.5 ± 5.1 hours, P=0.038; Group B vs Group C: 20.3 ± 8.2 hours vs 16.5 ± 5.1 hours, P=0.034). Oxycodone alone provides superior early postoperative analgesia compared to fentanyl-remifentanil in laparoscopic myoma surgery but may delay bowel recovery.

Xanthohumol Promotes Skp2 Ubiquitination Leading to the Inhibition of Glycolysis and Tumorigenesis in Ovarian Cancer

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.

High keratin 15 expression reflects favorable prognosis in early cervical cancer patients

Keratin 15 (KRT15) exhibits inconsistent prognostic roles in different cancers, and its prognostic value in early cervical cancer patients who receive tumor resection remains unknown. This study aimed to assess the relationship of KRT15 expression with prognosis in these patients. Totally, 147 early cervical cancer patients who received tumor resection were reviewed in this retrospective study. KRT15 was detected in formalin-fixed paraffin-embedded tumor tissue by immunohistochemistry (IHC). KRT15 IHC scores were computed by multiplying the percentage of positively stained cells (scored as 0-4) and corresponding staining intensity (scored as 0-3), ranging from 0 to 12. Elevated KRT15 IHC score was linked with moderate to well differentiation (P = 0.005), tumor size ≤ 4 cm (P = 0.017), and International Federation of Gynecology and Obstetrics (FIGO) stage Ia/Ib (P  0.05). KRT15 IHC score ≥ 3 and KRT15 IHC score ≥ 6 could not predict DFS or OS (all P > 0.05). By subgroup analyses, KRT15 IHC score ≥ 1 forecasted favorable DFS in patients with age > 45 years, human papillomavirus-positive, squamous carcinoma, and tumor size ≤ 4 cm (all P < 0.05). KRT15 IHC score ≥ 1 and KRT15 IHC score ≥ 3 predicted ascended DFS in patients without adjuvant radiotherapy or adjuvant chemotherapy (all P < 0.05). High KRT15 expression reflects favorable tumor features and longer survival in early cervical cancer patients who receive tumor resection.