Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

Abstract

Studies have found that circRnA in exosomes is associated with oral squamous cell carcinoma (oScc) progression. In this study, we examined the expression of circ_0000199 in circulating exosomes from patients with oScc and its role in the evaluation of relapse and prognosis. Real-time quantitative reverse transcription-polymerase chain reaction was performed to assess circ_0000199 expression in circulating exosomes from 108 patients with OSCC and 50 healthy people. Gain-and loss-functional experiments were performed to assess the role of circ_0000199 on cell proliferation and apoptosis in OSCC cells. Our results showed that the high level of circ_0000199 in circulating exosomes was significantly associated with betel quid chewing, tumor size, lymphatic metastasis, and TNM stage in patients with OSCC. In addition, the patients with high exosomal circ_0000199 had higher tumor recurrence rate and higher mortality rate than the patients with low exosomal circ_0000199. Overexpression of circ_0000199 promoted, while knockdown of circ_0000199 inhibited OSCC cell growth. Bioinformatics analysis predicted that circ_0000199 interacted with miR-145-5p and miR-29b-3p simultaneously, which were involved in multiple tumor-related signaling pathways. in conclusion, upregulation of circ_0000199 in circulating exosomes from patients with OSCC is positively associated with poor survival outcome. Circulating exosomal circ_0000199 can be used as a biomarker and potential therapeutic target for oScc. Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the world, accounting for 3% of malignant tumors 1. Although the treatment of OSCC has made breakthroughs in the past decades, the 5-year mortality rate is still less than 50% 2. Early diagnosis and early treatment are the keys to improve the survival rate of patients with OSCC. Exosomes have phospholipid bilayer membrane with the markers TSG101 and CD63. The size of exosomes ranges from 30 to 100 nm. These vesicles exist in almost all body fluids of the human body, including blood, serum, saliva, cerebrospinal fluid, and urine 3. Exosomes contain various substances, such as proteins, DNA, microRNA (miRNA), circular RNA (circRNA). These molecules can be transported to regulate the signaling pathways of the recipient cells 4. CircRNAs are covalently formed from the ends of a single RNA molecule, without 5′ and 3′ ribonucleotide end, and circRNAs are expressed abundantly, conserved and stably in cells with temporal and spatial specificity 5. CircRNAs can bind to miRNAs to inhibit their functions. Therefore, circRNA is also called miRNA sponge. With the continuous understanding of circRNA, researchers have found that circRNAs are widely involved in the occurrence and development of physiology and disease as well as tumors 6. As a new type of regulatory endogenous RNA, circRNAs are expected to become a tumor diagnostic marker and therapeutic target due to its characteristics such as stability, conservation, and tissue-specific expression 7. For example, circRNA_...

Blocking circ-SCMH1 (hsa_circ_0011946) suppresses acquired DDP resistance of oral squamous cell carcinoma (OSCC) cells both in vitro and in vivo by sponging miR-338-3p and regulating LIN28B

“…Recently, several circRNAs had been declared to be oncogenic factors in OSCC, such as circ_0000199 [30], circ_0109291 [31], circ_0001821 [32], circ_0013339 [33], and circ_0011946 [18]. Here, we validated these circRNAs expression in this cohort of OSCC tissues, and there were three circRNAs including circ_0109291, circ_0001821 and circ-SCMH1 that were upregulated in DDP-resistant OSCC tissues.…”

The Role of circRNAs in Human Papillomavirus (HPV)-Associated Cancers

“…Consequently, they can be used as therapeutic targets in treatment. As circRNAs are very resistant to ribonucleases [ 72 ], act both in cells and tissues in a specific way, and are stably expressed in biological fluids and exosomes [ 73 , 74 , 75 ], they could be potential biomarkers in the diagnosis and prognosis of various diseases, including cancers. Recent studies have elucidated the molecular mechanisms responsible for gastric cancer mediated by circRNAs [ 163 , 164 ].…”

“…circRNAs are insensitive to the action of ribonucleases [ 72 ], and their levels of expression are lower than those of mRNAs [ 27 , 54 , 65 ]. However, circRNAs act in cells and tissues in a type-specific manner and are stably expressed in saliva, blood, tissues, and exosomes [ 73 , 74 , 75 ]. For all these characteristics, ribonucleases resistance, tissue and type-specific function, and the presence in biological fluids, the circRNAs could be biomarkers in the diagnosis and prognosis of various diseases [ 76 , 77 ].…”

Circular RNA as a Potential Biomarker for Melanoma: A Systematic Review

“…In patients with oral squamous cell carcinoma, elevated circ_0000199 in circulating exosomes is positively associated with tumor size, lymphatic metastasis, TNM stage, higher recurrence and mortality rate, and poor survival outcome. Bioinformatics analysis predicts that circ_0000199 could affect multiple tumor-related signaling pathways by simultaneously interacting with miR-145-5p and miR-29b-3p (Luo et al, 2020 ). circRNAs appear to be highly conserved across mammals, and exosomal circRNAs are detected in bovine milk by high-throughput RNA sequencing analysis.…”