MicroRNA-200b inhibits epithelial-mesenchymal transition and migration of cervical cancer cells by directly targeting RhoE

Abstract

Previous studies have identified microRNA-200b (miR-200b) as a powerful regulator of epithelial-mesenchymal transition (EMT) via the control of gene expression. EMT is a critical event that is associated with the initiation of malignant tumor metastasis. A lack of E-cadherin expression and overexpression of vimentin are hallmarks of EMT. It is well‑known that RhoE, which is associated with regulation of the actin cytoskeleton and migration via alterations in cell motility, regulates the expression of E-cadherin, matrix metalloproteinase-9 (MMP-9) and vimentin. However, it remains to be elucidated whether miR‑200b may alter the molecular behavior of RhoE. The present study aimed to determine whether miR‑200b was able to regulate the EMT of cervical cancer, in order to control metastasis. In addition, the correlation between miR‑200b and RhoE, E‑cadherin and vimentin expression was investigated. Notably, miR‑200b was shown to inhibit the function of RhoE and suppress the EMT of cervical cancer. Furthermore, HeLa cells were transfected with miR‑200b mimics or inhibitors, and the protein expression levels of E‑cadherin, MMP‑9, vimentin and RhoE were subsequently detected. A Transwell assay was also conducted, in order to observe the metastatic ability of the HeLa cells. In addition, a luciferase reporter assay was performed using luciferase reporter vectors containing the full length 3'‑untranslated region (UTR) of RhoE; miR‑200b was able to significantly suppress relative luciferase activity by targeting the 3'‑UTR of RhoE. These results suggested that miR‑200b may markedly inhibit metastatic potential by regulating cell EMT and inhibiting RhoE; therefore, miR-200b may be considered an effective target for the treatment of patients with highly metastatic cervical cancer.

Substrate stiffness affects epithelial-mesenchymal transition of cervical cancer cells through miR-106b and its target protein DAB2

“…It is well acknowledged that microRNA is closely related to pathological process of several kinds of cancers such as cervical cancer (17,18). Importantly some studies have found that specific microRNA can regulate EMT of tumor cells (25)(26)(27)(28)(29)(30)(31)(32). In the present study, we found that miR-106b and its target protein DAB2 play significantly important regulatory roles in EMT process of cervical cancer cell lines SiHa and HeLa.…”

MicroRNAs in gynecological cancers: Small molecules with big implications

“…A number of miRNAs have been demonstrated to regulate EMT, thereby playing a role in the regulation of invasion and metastasis. miR-200 family, a known family of tumor suppressor miRNAs with well characterized role in EMT of cancer cells [202], has been implicated in EMT of OC cells [203, 204] as well as CC cells [205, 206]. Another member of this family, miR-429, has also been shown to reverse EMT [207].…”

Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development

“…miR-200a has been reported overexpressed in serum [71] whereas miR-200b has a controversial reported expression, while Cheng et al [119] and Cheng et al reported [120] a down-regulation, Zeng et al reported an up-regulation [121]. miR-200b mimic reduces migration and it seems that its overexpression inhibits EMT because E -cadherin is augmented and vimentin a matrix metalloproteinase-9 is decreased [119] by targeting RhoE directly which binds Guanosine-5’-triphosphate (GTP) but has no GTPase activity, and appears to act as a negative regulator of cytoskeletal organization leading to loss of adhesion, favoring migration and invasion [120]. On the other hand, miR-200b inhibition inhibits cell migration, invasion and tumor growth by targeting Forkhead Box G1 (FoxG1) a transcriptional repressor [121].…”