Effects of miR-330-3p on Invasion, Migration and EMT of Gastric Cancer Cells by Targeting PRRX1-Mediated Wnt/β-Catenin Signaling Pathway.
miRNA, as a biological marker, had more and more attention in recent years due to the important role it plays in cancer. Currently, there are extensive studies on miRNAs, among which miR-330-3p is reported to be implicated in the pathophysiological processes of various cancers. However, little progress has been made in the mechanism of miR-330-3p in gastric cancer.
To explore the expression and relevant mechanism of miR-330-3p and PRRX1 in gastric cancer (GC).
Forty-five GC patients (study group), from whom paired GC and paracancerous tissues were collected, and another 45 healthy subjects (control group) who underwent physical examination during the same period were enrolled. In addition, GC cells and human gastric mucosa cells were purchased, and miR-330-3p-mimics, miR-330-3p-inhibitor, miR-NC, si-PRRX1, and sh-PRRX1 were transfected into MKN45, SGC7901 cell. QRT-PCR was employed to assess the miR-330-3p and PRRX1 expressions in the samples, and the cell expressions of PRRX1, GSK-3β, p-GSK-3β, β-catenin, p-β-catenin, cyclin D1, N-cadherin, E-cadherin and vimentin were evaluated by Western blot (WB). MTT, Transwell and wound-healing experiments were adopted to detect cell proliferation, invasion and migration.
MiR-330-3p was under-expressed, while PRRX1 was highly expressed in the serum of patients, both of which had an area under the curve (AUC) of more than 0.9. MiR-330-3p and PRRX1 were associated with tumor diameter, TNM staging, lymph node metastasis and differentiation of GC patients. Overexpression of miR-330-3p and inhibition of PRRX1 expression could suppress epithelial-mesenchymal transition (EMT), proliferation, invasion and apoptosis of cells. What is more, WB assay showed that overexpressed miR-330-3p and inhibited PRRX1 could inhibit the expression levels of p-GSK-3β, β-catenin, cyclin D1, N-cadherin and vimentin proteins, while elevating GSK-3β, p-β-catenin and E-cadherin protein expressions. Dual-luciferase reporter assay confirmed that there was a targeting relation between miR-330-3p and PRRX1. Furthermore, rescue experiments revealed that the cell proliferation, invasion, migration did not differ significantly between co-transfected miR-330-3p-mimics+sh-PRRX1, miR-330-3p-inhibitor+si-PRRX1 groups of MKN45 and SGC7901 and the miR-NC group (without transfected sequences).
Overexpressed miR-330-3p can promote cell EMT, proliferation, invasion and apoptosis through inhibiting PRRX1-mediated Wnt/β-catenin signaling pathway, which is expected to be a potential therapeutic target for GC.
Ma B
，Ma J
，Yang Y
，He X
，Pan X
，Wang Z
，Qian Y
... -
《OncoTargets and Therapy》
miR-6838-5p Affects Cell Growth, Migration, and Invasion by Targeting GPRIN3 via the Wnt/β-Catenin Signaling Pathway in Gastric Cancer.
Gastric cancer (GC) is a highly prevalent digestive malignant tumor, ranking second in the tumor-related mortality globally. The microRNAs have been confirmed to be connected with GC progression. Accumulative evidence has suggested that miR-6838-5p exerts a suppressive effect on human cancers. Nonetheless, whether miR-6838-5p is involved in the regulation of GC remains to be investigated. During our research, miR-6838-5p was downregulated in GC cells. Upregulated miR-6838-5p repressed GC cell cycle progression, proliferation, migration, and invasion. Furthermore, miR-6838-5p overexpression repressed the nuclear import of β-catenin, thus inactivating Wnt/β-catenin pathway. Moreover, we observed that GPRIN3 was targeted by miR-6838-5p in GC with luciferase reporter and RIP assays. GPRIN3 upregulation reversed the suppression of miR-6838-5p in GC cellular processes. These findings suggest miR-6838-5p restrains the malignant behaviors of GC cells via targeting GPRIN3 to repress Wnt/β-catenin signaling pathway, which may provide novel targets for GC treatment.
Zhou W
，Ding X
，Jin P
，Li P
... -
《-》
LINC00689 participates in proliferation, chemoresistance and metastasis via miR-31-5p/YAP/β-catenin axis in colorectal cancer.
As a kind of high-incidence malignant tumors in the digestive tract, colorectal cancer (CRC) has extremely morbidity and mortality in the population. LncRNAs have been proved to regulate the proliferation, chemoresistance and metastasis of tumors including CRC. LINC00689 and miR-31-5p in CRC were found misregulated in CRC by TCGA analysis. However, the mechanism of LINC00689 and miR-31-5p in regulating CRC remains unknown. The expression levels of LINC00689, miR-31-5p and LATS2 in CRC tissues and cell lines were examined by qRT-PCR assay. Cell proliferation, metastasis (including invasion and migration) were quantified by MTT assay, colony formation and Transwell assay, respectively. Western blotting assay was then performed to verify the levels of YAP/β-catenin and metastasis-related proteins. Dual-luciferase reporter assay and RIP assay were performed to evaluate the interaction between LINC00689 (LATS2) and miR-31-5p. Moreover, the function of LINC00689 and miR-31-5p were confirmed by CRC xenograft in nude mice. LINC00689 was decreased while miR-31-5p was increased in CRC. The overexpression of LINC00689 or the knockdown of miR-31-5p inhibited cell proliferation, chemoresistance and metastasis of CRC cells. Meanwhile, the up-regulated LATS2 suppressed the activity of YAP/β-catenin pathway to repress CRC occurrence. Silencing LATS2 reversed the inhibition effects of overexpression of LINC00689 or knockdown of miR-31-5p on proliferation, chemoresistance and metastasis of CRC cells. LINC00689 indeed acted as a miR-31-5p sponge to inhibit CRC proliferation, chemoresistance and metastasis through up-regulating LATS2 and repressing YAP/β-catenin signaling pathway.
Du YL
，Liang Y
，Shi GQ
，Cao Y
，Qiu J
，Yuan L
，Yong Z
，Liu L
，Li J
... -
《-》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
