Lifeng Wang

LINC00958 facilitates cervical cancer cell proliferation and metastasis by sponging miR‐625‐5p to upregulate LRRC8E expression

AbstractAccepted as a malignant tumor worldwide, cervical cancer (CC) has attracted much attention for its high incidence and mortality rates. Previous studies have elucidated the critical regulatory function that long noncoding RNAs (lncRNAs) exert on the tumorigenesis and progression of diverse tumors. Although multiple investigations have depicted that LINC00958 has a great impact on the complex biological process of many cancers, knowledge concerning the regulatory role of LINC00958 in CC remains limited and needs to be further explored. In our study, LINC00958 expression was evidently overexpressed in CC tissues and cells. Besides this, LINC00958 negatively regulated miR‐625‐5p expression and was verified to bind with miR‐625‐5p in CC. Subsequently, it was testified by a series of experiments that LINC00958 promotes CC cell proliferation and metastasis by sponging miR‐625‐5p. Furthermore, the leucine‐rich repeat containing the eight family member E (LRRC8E) could bind with miR‐625‐5p, and its expression was negatively modulated by miR‐625‐5p, whereas positively regulated by LINC00958 in CC. Final rescue assays verified the effects of LINC0095/LRRC8E interaction and miR‐625‐5p/LRRC8E interaction on CC cell proliferation and metastasis. Collectively, LINC00958 facilitates CC cell proliferation and metastasis via the miR‐625‐5p/LRRC8E axis.

Combined delivery of salinomycin and docetaxel by dual-targeting gelatinase nanoparticles effectively inhibits cervical cancer cells and cancer stem cells

Intra-tumor heterogeneity is widely accepted as one of the key factors, which hinders cancer patients from achieving full recovery. Especially, cancer stem cells (CSCs) may exhibit self-renewal capacity, which makes it harder for complete elimination of tumor. Therefore, simultaneously inhibiting CSCs and non-CSCs in tumors becomes a promising strategy to obtain sustainable anticancer efficacy. Salinomycin (Sal) was reported to be critical to inhibit CSCs. However, the poor bioavailability and catastrophic side effects brought about limitations to clinical practice. To solve this problem, we previously constructed gelatinase-stimuli nanoparticles composed of nontoxic, biocompatible polyethylene glycol-polycaprolactone (PEG-PCL) copolymer with a gelatinase-cleavable peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG) inserted between the two blocks of the copolymer. By applying our "smart" gelatinase-responsive nanoparticles for Sal delivery, we have demonstrated specific accumulation in tumor, anti-CSCs ability and reduced toxicity of Sal-NPs in our previous study. In the present study, we synthesized Sal-Docetaxel-loaded gelatinase-stimuli nanoparticles (Sal-Doc NP) and confirmed single emulsion as the optimal method of producing Sal-Doc NPs (Sal-Doc SE-NP) in comparison with nanoprecipitation. Sal-Doc SE-NPs inhibited both CSCs and non-CSCs in mice transplanted with cervical cancer, and might be associated with enhanced restriction of epithelial-mesenchymal transition (EMT) pathway. Besides, the tumorigenic capacity and growing speed were obviously suppressed in Sal-Doc-SE-NPs-treated group in rechallenge experiment. Our results suggest that Sal-Doc-loaded gelatinase-stimuli nanoparticles could be a promising strategy to enhance antitumor efficacy and reduce side effects by simultaneously suppressing CSCs and non-CSCs.