Circular RNA LPAR3 sponges microRNA‐198 to facilitate esophageal cancer migration, invasion, and metastasis

Abstract

In this study, we explored expression and functions of circular RNA LPAR3 (circLPAR3) in esophageal squamous cell carcinoma (ESCC). The differential expression of circular RNAs (circRNAs) in 10 ESCC and corresponding paracarcinoma tissues was analyzed through circRNA microarray, then the candidate circRNAs were detected and verified through quantitative RT‐PCR, and a novel circRNA was screened, which was circLPAR3. Circular RNA LPAR3 showed apparently high expression in ESCC tissues and cells, which was closely correlated with the clinical stage and lymph node metastasis of ESCC patients. Circular RNA LPAR3 was mainly located in the cytoplasm of ESCC cells, which was more stable than the baseline gene. Circular RNA LPAR3 upregulated MET gene expression through sponge adsorption of microRNA (miR)‐198, activated the RAS/MAPK and the PI3K/Akt pathways, and promoted ESCC cell migration, invasion, and metastasis in vivo and in vitro. However, it had no effect on ESCC cell proliferation. Circular RNA LPAR3 can regulate the miR‐198‐MET signal axis to promote the migration, invasion, and metastasis of esophageal cancer cells, which can thereby serve as a potential diagnostic and therapeutic target of esophageal cancer.

CircRNA circ-OGDH (hsa_circ_0003340) Acts as a ceRNA to Regulate Glutamine Metabolism and Esophageal Squamous Cell Carcinoma Progression by the miR-615-5p/PDX1 Axis

“… 16 At present, many circRNAs have been uncovered to be implicated in the tumorigenesis of ESCC. It was reported that circRNA circ-GSK3β, 17 circRNA circ-LPAR3, 18 and circRNA circ-NTRK2 played a tumor-promoting role in ESCC, while circRNA circ-VRK1, 19 circRNA circ-SMAD7, 20 and circRNA circ-FOXO3 21 acted as a tumor suppressor. Even so, the exact mechanism of circRNAs in ESCC is still unknown.…”

CircRNAs: a new target for the diagnosis and treatment of digestive system neoplasms

“…In addition, some overexpressed circRNAs regulate biological processes in tumors through their own pathways; for example, circ_0003340 is overexpressed in ESCC and promotes tumor development through the miR-564/TPX2 pathway 34 . circLPAR3 upregulates MET gene expression by acting as a sponge for miR-198; activates the RAS/MAPK and PI3K/Akt pathways; and promotes the migration, invasion, and metastasis of ESCC cells in vivo and in vitro 35 . The expression of hsa_circ_0012563 in ESCC was significantly upregulated, while hsa_circ_0012563 knockout inhibited the XRCC1-mediated EMT pathway, which, in turn, inhibited cell migration and invasion 36 .…”

Research Progress of Circular RNA in Gastrointestinal Tumors

“…The conservation of circRNAs among different species indicates that circRNAs are not by-products of precursor mRNA splicing, suggesting circRNA is extremely important in certain biological processes. circRNAs are specifically expressed at the stage of tissue development, and are involved in innate immunity, development of the nervous system, metabolism of hormones in the body, as well as tumorigenesis and tumor progression (52)(53)(54)(55).…”

“…circRNA can act as miRNA sponge in GI tumors (Figure 3A). circLPAR3 is highly expressed in esophageal squamous cell carcinoma (ESCC) tissues and cells, which can upregulate the expression of c-MET through sponge adsorption of miR-198 to increase the migration and invasion of ESCC (55). circCCDC9, with low expression in gastric cancer tissues and cells, can attenuate the inhibitory effect on the target gene CAV1 after adsorbing miR-6792-3p, thereby inhibiting the proliferation, migration and invasion of gastric cancer cells (71).…”