Abstract
BackgroundIncreasing studies confirmed that abnormal lncRNAs expression play a critical role in cervical cancer (CC) development and progression. LncRNA TPT1-AS1, a novel lncRNA, its role and underlying mechanisms involved in CC remain largely unknown.MethodsColony formation, EdU and Transwell assays were used to determine colony formation, proliferation, migration and invasion in vitro. The subcutaneous tumor model and tail vein injection lung metastasis model were performed to check tumor growth and metastasis in vivo. Luciferase activity and RIP experiment were carried out to determine the interaction between miR-324-5p and TPT1-AS1.ResultsWe demonstrated for the first time that TPT1-AS1 expression was up-regulated in CC tissues and cell lines. High TPT1-AS1 was significantly correlated with adverse prognostic characteristics and poor survival. TPT1-AS1 overexpression and knockdown experiments revealed that TPT1-AS1 promoted cell colony formation, proliferation, migration, invasion and EMT progression of CC cells in vitro and in vivo. The underlying mechanism indicated that TPT1-AS1 functioned as an endogenous sponge for miR-324-5p in CC cells. Gain- and loss- experiment confirmed that miR-324-5p inhibited cell colony formation, proliferation, migration, invasion and EMT progression of CC cells, and mediated the biological effects of TPT1-AS1. Further investigations confirmed that SP1 was a direct target of miR-324-5p and mediated the effects of TPT1-AS1 and miR-324-5p in CC.ConclusionsWe demonstrated for the first time that TPT1-AS1 as an oncogenic lncRNA in CC progression and as a potential target for CC cure.
Highlights
Increasing studies confirmed that abnormal Long non-coding RNA (lncRNA) expression play a critical role in cervical cancer (CC) development and progression
Our results showed that TPT1-AS1 expression was significantly up-regulated in CC tissues compared to matched adjacent non-tumor tissues (P < 0.05, Fig. 1a)
TPT1-AS1 promotes cell colony formation, proliferation, migration and invasion in vitro and in vivo To observe the functional relevance of TPT1-AS1 in CC cells, we transfected C33A whose TPT1-AS1 was lowest with functional pcDNA/TPT1-AS1 and transfected
Summary
Increasing studies confirmed that abnormal lncRNAs expression play a critical role in cervical cancer (CC) development and progression. LncRNA TPT1-AS1, a novel lncRNA, its role and underlying mechanisms involved in CC remain largely unknown. Non-coding RNAs, which contains microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been recognized as novel candidates of signs or potential targets of treatment in multiple cancers [6,7,8]. Accumulating evidence reported that aberrant lncRNAs play critical roles in diverse biological courses including cellular differentiation, proliferation, apoptosis, migration, invasion and stem-cell biology [9,10,11,12,13]. Upregulation of lncRNA SNHG12 increased cell growth and invasion in cervical cancer through acting as a sponge for miR-424-5p [14]. The expression level and effects of TPT1-AS1 in CC remain largely unknown
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