circLPAR1 is a novel biomarker of prognosis for muscle‑invasive bladder cancer with invasion and metastasis by miR‑762

Abstract

Circular RNAs (circRNAs) are a specific form of non-coding RNAs, that serve a pivotal role in the development of human diseases, including Alzheimer's disease and cancer; however, only a few are known with respect to cancer. The present study identified a novel circRNA, circ lysophosphatidic acid receptor 1 (LPAR1) (hsa_circ_0087960), derived from two exons 226 base pairs in length, in muscle-invasive bladder cancer (MIBC) tissues. circLPAR1 was identified to be lowly expressed in MIBC tissues in a cohort of 125 cases, and predicted a poor disease-specific survival time, compared with patients with high circLPAR1 expression (52.4 vs. 56.0 months; P=0.001) by univariate and multivariate Cox regression analyses. Matrigel and wound healing assays also demonstrated that the invasion of 5637 and T24 bladder cancer cells were significantly enhanced following the knockdown of circLPAR1 by small interfering RNA (si-circLPAR1-1 in T24 cell line, P= 0.01; si-circLPAR1-2 in 5637 cell line, P= 0.003; si-circLPAR1-2 in T24 cell line, P= 0.002; si-circLPAR1-2 in 5637 cell line, P= 0.006). The bioinformatics analysis indicated that circLPAR1 may harbor specific microRNAs (miRNAs) according to the miRNAs seed sequence matching. A luciferase reporter assay revealed that miR-762 can inhibit the activity of the transfected luciferase gene when inserted in a circLPAR1 wild-type fragment, and this inhibition could be alleviated when the luciferase gene was inserted in a circLPAR1 fragment with the mutated miR-762 target site. In conclusion, the circLPAR1 may function as a potential novel and stable biomarker for the prognosis of MIBC and may be associated with the invasion and metastasis by miR-762.

circ_0067934 increases bladder cancer cell proliferation, migration and invasion through suppressing miR‑1304 expression and increasing Myc expression levels

“…In addition, it was suggested that circ_0067934 may be a therapeutic target and prognostic marker for bladder cancer, as the silencing of circ_0067934 inhibited the proliferative, migratory and invasive ability of bladder cancer cells. Notably, several other circRNAs have been reported to regulate bladder cancer, such as hsa_circ_0068871 and circRNA lysophosphatidic acid receptor 1 (20,21). Whether circ_0067934 expression is correlated with the expression of these reported circRNAs requires further investigation.…”

Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

“…In vitro and in vivo experiments further found that Cdr1as inhibits proliferation, invasion, and migration of BCa by binding to miR‐135a . In another study, circLPAR1 was found to be downregulated in MIBC tissues . Patients with low expression levels of circLPAR1 had shorter disease‐specific survival than patients with high expression levels .…”

“…Patients with low expression levels of circLPAR1 had shorter disease‐specific survival than patients with high expression levels . At the same time, it was found that circLPAR1 affected MIBC invasion and metastasis by sponging miR‐762 …”

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

“…152 Moreover, circLPAR1 inhibited the activity of miR-762 by directly binding to miR-762 thereby regulating invasion and metastasis of muscle-invasive bladder cancer cells. 153 circRNA-cTFRC regulated cell invasion and proliferation through acting as a ceRNA for miR-107 to affect the expression of TFRC expression in bladder cancer cells. 154 CircUBXN7 showed to inhibit the proliferation and invasion of bladder cancer cells through binding to miR-1247-3p to elevate the expression of β-1, 4-Galactosyltransferase III (B4GALT3), which is the direct target gene of miR-1247-3p.…”