Abstract
BackgroundCervical cancer (CC) is the second leading cause of cancer deaths in women worldwide, still lacking effective biomarkers and therapies for diagnosis and treatment. CircRNAs are a class of endogenous RNAs that regulate gene expression through interacting with miRNAs, implicating in the progression of cancers. Yet the roles of circRNAs in CC are not fully characterized.MethodsFifty pairs of tumor and adjacent normal tissues from CC patients, as well as four CC cell lines and a normal human cervical epithelial cell line were subjected to qRT-PCR assay to assess the mRNA levels of hsa_circ_0000069. CCK-8 and colony formation assays were conducted to detect the proliferation of CC cells. Transwell assay was used to evaluate the migration and invasion capabilities of CC cells. RNA pull-down and luciferase assays were used to determine the interaction between hsa_circ_0000069 and miR-873-5p. A xenograft model of CC was established to verify the in vivo function of hsa_circ_0000069 in CC progression.ResultsWe firstly demonstrated that hsa_circ_0000069 was significantly upregulated and closely related to the lymph node metastasis, and poor prognosis of CC patients. Besides, hsa_circ_0000069 promoted CC cell proliferation, migration, and invasion. The knockdown of hsa_circ_0000069 also inhibited CC tumor growth in vivo. Mechanically, we revealed that hsa_circ_0000069 functioned as an oncogene in CC, which is the sponge of miR-873-5p to facilitate the TUSC3 expression, consequently promoting CC progression.ConclusionWe demonstrated a critical hsa_circ_0000069-miR-873-5p-TUSC3 function network involved in the CC progression, which provides mechanistic insights into the roles of CircRNAs in CC progression and a promising therapeutic target for CC treatment.
Highlights
Cervical cancer (CC) is the second leading cause of cancer deaths in women worldwide, still lacking effective biomarkers and therapies for diagnosis and treatment
Increasing studies demonstrated that circRNAs regulate gene expression acting as competing endogenous RNA, known as microRNAs sponges, which sequester miRNAs to terminate the regulation of their target genes [7,8,9,10,11]
CircRNA hsa_circ_0000069 is upregulated in CC and associated with CC progression To explore the biofunctions of CircRNAs in CC, the most differentially expressed CircRNAs in 5 pairs of CC tissues and para-tumor tissues data in GSE102686 were analyzed [23] (Fig. 1a)
Summary
Cervical cancer (CC) is the second leading cause of cancer deaths in women worldwide, still lacking effective biomarkers and therapies for diagnosis and treatment. CircRNAs are a class of endogenous RNAs that regulate gene expression through interacting with miRNAs, implicating in the progression of cancers. The underlying mechanism and novel biomarkers for CC are urgently needed. Circular RNAs (circRNAs) are a class of novel noncoding RNAs, characterized by a covalently closed continuous loop without any 50 to 30 polarity or a polyadenylated tail [5, 6]. CircRNAs play a key role in various biological processes, such as cell proliferation and metastasis [12], and act as potential biomarkers in many diseases including cancers [13,14,15,16,17,18,19,20,21]. Further investigation of circRNAs will enable us to better understand the tumorigenesis and improve the diagnosis and therapies of cancers
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