Oncogenic long intervening noncoding RNA Linc00284 promotes c-Met expression by sponging miR-27a in colorectal cancer

Abstract

Emerging evidences suggest that long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and cancer progression. Here, the aim of this study is to investigate the biological function of long intervening noncoding RNA Linc00284 in colorectal cancer (CRC). The expression levels of Linc00284, miR-27a and c-Met were evaluated by qPCR and/or Western blotting. Immunohistochemistry was used to detect the expression of Ki67 and Phh3 in tumor tissues. The interaction between Linc00284, miR-27a and c-Met was validated by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell function experiments, including CCK-8, wound-healing and transwell invasion assays, were conducted. The in vivo studies were performed with the subcutaneous tumor xenograft mouse models. Our findings reveal that Linc00284 is upregulated in CRC tissues and colorectal cancer cell lines HCT116 and SW480 in comparison with corresponding para-carcinoma tissues and human fetal colonic mucosa cells FHC. High expression of Linc00284 in tumor tissues is associated with tumor metastasis and predicts a poor clinical outcome in CRC patients. Serum Linc00284 is increased, while miR-27a is decreased in CRC patients compared to healthy controls. ROC curve analysis indicates that serum Linc00284 and miR-27a produce the area under the curve (AUC) value of at 0.8151 and 0.7316 in patients with colorectal cancer compared to healthy individuals, respectively. Additionally, results in vitro and in vivo experiments suggest that Linc00284 silencing significantly suppresses CRC cell proliferation and/or invasion. Mechanistically, Linc00284 promotes c-Met expression by acting as miR-27a sponge, leading to the activation of downstream signaling pathways, thereby causing malignant phenotypes of CRC cells. Taken together, Linc00284 exhibits oncogenic function and the disturbance of Linc00284/miR-27a/c-Met regulatory axis contributes to CRC progression, providing new insight into the pathogenesis of colorectal cancer. Importantly, the expression levels of serum Linc00284 and miR-27a may serve as clinical biomarkers for CRC diagnosis.

Ferroptosis-related lncRNA signature predicts the prognosis and immune microenvironment of hepatocellular carcinoma

“…The transcription length exceeds 200 nucleotides and lacks a complete open reading frame (ORF). Furthermore, lncRNAs play a vital role in the progression of various cancers 18 – 20 . H19, HULC, HEIH, linc00152, and MVIH, are highly upregulated lncRNAs and valuable biomarkers in HCC 21 .…”

A genome-wide expression profile of noncoding RNAs in human osteosarcoma cells as they acquire resistance to cisplatin

“…Importantly, we observed that the majority of dysregulated lncRNAs in OS-R (Table 14 ) are unique and have not been previously reported for drug resistance, thus providing a pool of markers that can be explored in the future for their putative functional role in osteosarcoma and cisplatin resistance. Interestingly, LINC00284, which was highly upregulated in OS-R, was previously correlated with the promotion of cellular proliferation, invasion, migration, and angiogenesis and the negative regulation of apoptosis-related pathways in a recent study, indicating a probable role that it might play in cisplatin resistance in OS cells [ 64 ]. Furthermore, despite the limited number of miRNAs being upregulated, we observed that hsa-miR-30c-1-3p, hsa-miR-19a-3p, hsa-miR-5582-3p and hsa-miR-615-3p showed inverse correlations in expression with key genes that were expressed in OS-R cells.…”

ALDH1A3–Linc00284 Axis Mediates the Invasion of Colorectal Cancer by Targeting TGFβ Signaling via Sponging miR-361-5p

“…Linc00284 shRNA, mimic and inhibitor of miR-361-5p, full-length of ALDH1A3 and Linc00284, and negative controls were ordered from Genechem (Shanghai, China). The stable ALDH1A3 knockdown and Linc00284 knockdown SW480 cells were established by using the corresponding lentivirus generated from HEK293T cells as described previously [ 12 ]. Lentivirus expression and package vectors, pLVX pVSVG, pRSV-REV, and pMDLg/pRRE were purchased from Genechem.…”