Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1

Abstract

The aims of this study were to discover if increased circulating microRNA-21 (miR-21) expression in serum is associated with lymph node metastasis in patients with cervical cancer and look further into the molecular mechanism of these. Whole-blood samples from 89 patients who have been histopathologically confirmed as having cervical cancer and 20 control subjects were collected, and then the association between lymph node metastasis and the level of circulating miR-21 was compared. Then cervical cancer cell lines HeLa (HPV-18 DNA, E6/E7RNA) and HT-3 (HPV DNA, E6/E7RNA) were used to confirm the interaction between miR-21 and RASA1. The role of RASA1 in cervical cancer cell migration was also studied in HeLa. Increased circulating miR-21 expression in serum is associated with lymph node metastasis in patients with cervical cancer. MicroRNA-21 reduces RASA1 expression in cervical cancer cell lines and promotes cervical cancer cell migration via RASA1. Furthermore, Ras-induced epithelial-mesenchymal transition contributes to miR-21/RASA1 axis promoting cervical cancer cell migration. Circulating miR-21 in serum could be a promising biomarker in auxiliary diagnosis of lymph node metastasis in cervical cancer, and inhibition of miR-21/RASA1 axis could be a possible strategy to restrain migration of cervical cancer.

Down-regulation of RASA1 Is Associated with Poor Prognosis in Human Hepatocellular Carcinoma

“…RASA1 is ubiquitously expressed across different tissue types. Although previous studies revealed that RASA1 may play tumor suppressive roles in many cancer types (12,14,15), the correlation between the role of RASA1 expression, tumor differentiation and overall survival in HCC have not been previously addressed in detail. This study shows that RASA1 protein is rarely expressed in HCC, especially in poor differentiated and undifferentiated tumors or large-sized tumors.…”

“…RASA1 has been involved in many biological processes including actin filament polymerization, cellular apoptosis, and cell migration (13). Besides, several studies indicated that onco-microRNAs (micorRNA-21 and micorRNA-182) can promote tumor angiogenesis or lymph node metastasis by targeting RASA1 (14,15). Therefore, RASA1 functions as a tumor suppressor in several types of cancer.…”

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

“…Ten of 15 included studies had selected circulating HPV DNA as a detected gene target. Other gene targets had higher sensitivity but lower specificity, including SIM1 methylation [26], MEG3 methylation [28], Bmi-1 [29], miR-21 [30], and hsa-miR-92a [31].…”

“…Polymerase chain reaction (PCR) was mainly applied to detect ctDNA in the studies included in this analysis. Two studies [10,27] used Taqman PCR, and another three studies [29][30][31] used reverse transcription PCR. Additionally, two studies [17,32] used droplet digital PCR (ddPCR), and three studies [24,26,28] used methylation-specific (MSP) PCR.…”

“…Circulating HPV DNA or viral-cellular junction was detected in six studies [10,17,24,27,32,33]. Other target genes were also different, such as Bmi-1 mRNA [29], miR-21 [30], PIK3CA mutations [34], hsa-miR-92a [31], and SIM1 methylation [26]. Nine of the studies extracted ctDNA from plasma, and the other six studies extracted DNA from serum.…”