Abstract
Background/AimsLong non-coding RNAs (lncRNAs) play important roles in many diseases and participate in posttranscriptional regulatory networks in tumors. However, the functions of major lncRNAs in cervical cancer are unclear. Therefore, the aim of this study was to construct a lncRNA-mRNA coexpression functional network and analyze lncRNAs that might contribute to the pathogenesis of cervical cancer.MethodsDifferentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between three pairs of cervical cancer tissues and adjacent mucosa were identified by lncRNA microarray analysis. LncRNA-mRNA correlation analysis and functional enrichment were performed on the DEGs. From the correlation network, PCBP1-AS1 was selected as a candidate for further analysis. PCBP1-AS1 expression was examined by qPCR, and Kaplan–Meier survival, clinicopathology, GSEA, and immune infiltration analysis of PCBP1-AS1 were performed. The immune responses of PCBP1-AS1 expression in cervical cancer were analyzed using TIMER and western blot. PCBP1-AS1 was knocked down and overexpressed to evaluate its role in cell proliferation, migration, and invasion.ResultsA total of 130 lncRNAs were significantly differentially expressed in cervical cancer patient samples compared with control samples. Differentially expressed mRNAs in the lncRNA-mRNA interaction network were involved in the EMT process. Combined with the Kaplan–Meier survival analyses, the coexpression network revealed that PCBP1-AS1 was significantly associated with OS and clinicopathological parameters in cervical cancer patients. Moreover, PCBP1-AS1 expression was not only significantly increased in cervical cancer specimens but also associated with tumor stage, TNM, and invasion. GSEA revealed that PCBP1-AS1 is closely correlated with cell biological function via the p53 and notch signaling pathways. TIMER analysis revealed that the numbers of NK cells and M2 macrophages decreased when PCBP1-AS1 expression was high, which was consistent with the western blot results in clinical samples. Furthermore, in vitro experiments showed that high expression of PCBP1-AS1 promoted cell proliferation, migration, and invasion.ConclusionsTranscriptomic and lncRNA-mRNA correlation analyses revealed that PCBP1-AS1 plays a key role as an independent prognostic factor in patients with cervical cancer. The identification of PCBP1-AS1 as a new biomarker for cervical cancer could help explain how changes in the immune environment promote cervical cancer development.
Highlights
Cervical cancer is one of the most common malignancies in females, and it has the highest mortality among female reproductive system malignancies [1, 2]
A series of studies have indicated that lncRNAs exert substantial effects on the pathogenesis of carcinomas, suggesting that lncRNAs might act as prognostic indicators in tumorigenesis and cancer development [14,15,16]
PSMB8-AS1 contributes to pancreatic cancer progression by modulating the miR-382-3p/STAT1/PD-L1 axis [21]
Summary
Cervical cancer is one of the most common malignancies in female patients, and it has the highest mortality of all female reproductive system malignancies [1, 2]. Most patients suffering from cervical cancer are diagnosed at advanced stages, accompanied by invasion and distant metastasis [4, 5]. Some progress has been made in research on the mechanism of cervical cancer, clinical applications are still limited, resulting in persistently high mortality in cervical cancer [8, 9]. The discovery of new mechanisms associated with cervical cancer for the identification of useful biomarkers as well as new specific therapeutic targets in cervical cancer is urgently needed
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