CircularRNA circSLC8A1 acts as a sponge of miR-130b/miR-494 in suppressing bladdercancer progression viaregulating PTEN

Lu Q¹, Liu T¹, FengH², Yang R¹, Zhao X¹, Chen W¹, JiangB¹, Qin H¹, Guo X², Liu M², LiL², Guo H³.

Mol?Cancer. Pub date:2019-6-22

doi: 10.1186/s12943-019-1040-0.

Abstract

BACKGROUND:

Circular RNAs (circRNAs) are a novel class of endogenousnoncoding RNAs formed by a covalently closed loop, and increasing evidence hasrevealed that circRNAs play crucial functions in regulating gene expression.CircSLC8A1 is a circRNA generated from the SLC8A1 gene. Currently, the role andunderlying molecular mechanisms of circSLC8A1 in bladder cancer remain unknown.

METHODS:

The differentially expressed circRNAs were identified fromRNA-sequencing data, and circSLC8A1 was determined as a new candidate circRNA.qRT-PCR was used to detect the expression of circRNAs, miRNAs and mRNAs inhuman tissues and cells. RNA pull-down assay and luciferase reporter assay wereused to investigate the interactions between the specific circRNA, miRNA andmRNA. The effects of circSLC8A1 on bladder cancer cells were explored bytransfecting with plasmids in vitro and in vivo. The expression of PTEN wasdetected by Western blot. The biological roles were measured by wound healingassay, transwell assay, and CCK-8 assay.

RESULTS:

In the present study, we found that circSLC8A1 wasdown-regulated in bladder cancer tissues and cell lines, and circSLC8A1expression was associated with the pathological stage and histological grade ofbladder cancer. Over-expression of circSLC8A1 inhibited cell migration,invasion and proliferation both in vitro and in vivo. Mechanistically,circSLC8A1 could directly interact with miR-130b/miR-494, and subsequently actas a miRNA sponge to regulate the expression of the miR-130b/miR-494 targetgene PTEN and downstream signaling pathway, which suppressed the progression ofbladder cancer.

CONCLUSIONS:

CircSLC8A1 acts as a tumor suppressor by a novelcircSLC8A1/miR-130b, miR-494/PTEN axis, which may provide a potential biomarkerand therapeutic target for the management of bladder cancer.

推薦理由：

1.CircSLC8A1是由SLC8A1基因產(chǎn)生的circRNA。目前，circSLC8A1在膀胱癌中的作用和潛在分子機制尚不清楚。越來越多的證據(jù)表明circRNA在調(diào)節(jié)基因表達中起著至關(guān)重要的作用。

2.實驗方法和研究思路值得學(xué)習(xí)。

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