Long non-coding RNA LINC00649 regulates YES-associated protein 1 (YAP1)/Hippo pathway to accelerate gastric cancer (GC) progression via sequestering miR-16-5p

Abstract

Although long non-coding RNA (LncRNA) LINC00649 is reported to be closely associated with acute myeloid leukemia (AML), prostate cancer and colorectal cancer, its role in regulating other types of cancer, such as gastric cancer (GC), has not been studied. This study analyzed the expression status of LINC00649 in GC tissues and cells by performing Real-Time qPCR analysis, and we found that LINC00649 tended to be enriched in cancerous tissues and cells but not in their normal counterparts, which were supported by the data from TCGA dataset. Next, by performing the gain-and loss-of-function experiments, we expectedly found that LINC00649 acted as an oncogene to accelerate GC cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro and promote its tumorigenesis in vivo. Moreover, the online miRDB software predicted that miR-16-5p bound to both LINC00649 and 3 untranslated region (3 UTR) of YAP1 mRNA, which were validated by the following dual-luciferase reporter gene system assay and RNA pull-down assay. Finally, we proved that LINC00649 exerted its tumor-promoting effects in GC by regulating the miR-16-5p/YES-associated protein 1 (YAP1)/Hippo pathway. Mechanistically, knock-down of LINC00649 suppressed YAP1 expressions by releasing miR-16-5p, resulting in the recovery of the Hippo pathway, which suppressed the expression levels of the downstream oncogenes, including EGFR, SOX2 and OCT4, leading to the inhibition of the malignant phenotypes in GC cells. In conclusion, this study, for the first time, evidenced that LINC00649 promoted GC progression by targeting the miR-16-5p/YAP1/Hippo signaling pathway, which provided potential diagnostic and therapeutic indicators for GC treatment for clinical utilization.

Long non-coding RNA LOC107985656 represses the proliferation of hepatocellular carcinoma cells through activation of the tumor-suppressive Hippo pathway

“…Accumulated evidence shows that Hippo signaling is a key regulator, and activation of the Hippo pathway acts as a tumor-suppressive in several human cancers, for example, gastric cancer [ 15 ], lung cancer [ 16 ], and HCC [ 17–20 ], etc. YAP and TAZ, the effectors of the Hippo pathway, are transcription co-activators that serve as oncogenes in tumorigenesis and development in several cancers [ 21 ].…”

Myosin light chain 9 promotes the proliferation, invasion, migration and angiogenesis of colorectal cancer cells by binding to Yes-associated protein 1 and regulating Hippo signaling

“…It has been well reported that YAP1 is a transcriptional coactivator of the Hippo pathway that plays an oncogenic role in a variety of malignancies [ 32–34 ]. Dysregulation of the Hippo pathway may induce tumor development, including colorectal, lung, liver and gastric cancers [ 35 , 36 ]. In our experiments, MYL9 was found to promote proliferation, invasion, migration, angiogenesis in colorectal cancer cells via binding to YAP1 and regulating Hippo signaling.…”

Analysis and prognostic significance of tumour immune infiltrates and immune microenvironment of m6A-related lncRNAs in patients with gastric cancer

“…For example, Ning Cui experimentally observed [ 24 ] that LINC00511 acted as a therapeutic target in GC treatment and could regulate the expression of STAT3 via miR-625-5p. LINC00649 functions as an oncogenic lncRNA by accelerating cell proliferation, migration and epithelial–mesenchymal transition [ 25 ]. With the continuous development of molecular biotechnology, lncRNAs related to GC have been discovered, but our understanding of them is still in rudimentary stages.…”