ABSTRACT
Long non-coding RNAs (lncRNAs) play key roles in cancer development and progression. However, the biological function and clinical significance of most lncRNAs in cervical cancer remain elusive. In this study, we explore the function and mechanism of lncRNA surfactant associated 1 (SFTA1P) in cervical cancer. We firstly identified SFTA1P by analyzing the RNA sequencing data of cervical cancer from our previous study and from The Cancer Genome Atlas (TCGA). We then verified SFTA1P expression by qRT-PCR. The cell proliferation and migration capacity of SFTA1P was assessed by using CCK-8, colony formation, transwell and wound healing assays. RNA pull-down, RNA immunoprecipitation (RIP), RNA stability and western blot assays were used to reveal potential mechanisms. Athymic nude mice were used to evaluate tumorigenicity and metastasis in vivo. SFTA1P is upregulated in cervical tumor tissues and its high expression is associated with poor prognosis. Biologically, knockdown of SFTA1P inhibited the proliferation, migration, and invasion of cervical cancer cells in vitro, as well as tumorigenesis and metastasis in vivo. Mechanistically, SFTA1P was shown to interact with polypyrimidine tract binding protein 1 (PTBP1) to regulate the stability of tropomyosin 4 (TPM4) mRNA, thereby resulting in malignant cell phenotypes. TPM4 knockdown could attenuate the suppression of cell progression induced by either SFTA1P or PTBP1 knockdown. Our findings demonstrate that SFTA1P can promote tumor progression by mediating the degradation of TPM4 mRNA through its interaction with PTBP1 protein. This provides a potential therapeutic strategy to target the SFTA1P-PTBP1-TPM4 axis in cervical cancer.
Subject(s)
RNA, Long Noncoding , Uterine Cervical Neoplasms , Animals , Female , Humans , Mice , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Mice, Nude , Polypyrimidine Tract-Binding Protein/genetics , Polypyrimidine Tract-Binding Protein/metabolism , RNA Stability/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , Tropomyosin/genetics , Tropomyosin/metabolism , Uterine Cervical Neoplasms/pathologyABSTRACT
Immune challenge in early life has been observed to influence the long-term reproductive dysfunction. On PNDs 3 and 5, female offsprings were administered with LPS (50µg/kg, i.p.) or saline. Vaginal opening was recorded, and oestrous cyclicity was monitored immediately post puberty and again at 56-70 days. At 10 weeks of age, the ovaries were removed for immunostaining and RNA analysis. Neonatal exposure to LPS resulted in a significant delay puberty onset as well as destroyed expression of ovulation related genes. At PND 42 and 70, a significant increase in Kiss1 mRNA and Kisspeptin expression was detected at proestrus and oestrus in neo-LPS treated rats compared with the counterparts. Therefore, neonatal LPS exposure had a long-term effect on reproductive function and the up-regulated expression of ovarian Kiss1 and kisspeptin during the ovulatory transition stage may contribute to ovulatory dysfunction induced by peripheral LPS administration in early life.
