CCL18-induced LINC00319 promotes proliferation and metastasis in oral squamous cell carcinoma via the miR-199a-5p/FZD4 axis

Abstract

Long non-coding RNAs (lncRNAs), which may be modulated by chemokines, are key regulators in many cancers including oral squamous cell carcinoma (OSCC). An understanding of lncRNAs involved in chemokine (CC motif) ligand 18 (CCL18)-induced OSCC promotion remains elusive. The present study using lncRNA sequencing found LINC00319 to be significantly upregulated in OSCC cells subjected to rCCL18 stimulation. Furthermore, LINC00319 knockdown was found to attenuate the carcinogenic function of CCL18 in OSCC, reducing OSCC proliferation, metastasis, epithelial-mesenchymal transition (EMT), and angiogenesis. LINC00319 was demonstrated to act as a ceRNA in OSCC, which directly responded to miR-199a-5p and rescued the repression of FZD4 by miR-199a-5p. Functionally, in vitro and in vivo experiments showed that LINC00319 promoted OSCC growth and metastasis via downregulating miR-199a-5p and upregulating FZD4. In vitro rescue assays demonstrated that miR-199a-5p inhibitor or FZD4 overexpression reversed the effects of LINC00319 silencing in OSCC. Importantly, the expression of miR-199a-5p and FZD4 were found to be mediated by CCL18, and miR-199a-5p mimics inhibited the CCL18-promoting effects in oral cancer cells. Taken together, these results evidenced a mechanism of CCL18 action in OSCC mediated through the LINC00319/miR-199a-5p/FZD4 signaling pathway, which may comprise a potential target for OSCC therapeutic development.

Long non-coding RNA LINC01207 promotes cell proliferation and migration but suppresses apoptosis and autophagy in oral squamous cell carcinoma by the microRNA-1301-3p/lactate dehydrogenase isoform A axis

“…Accumulating evidence suggests that lncRNAs may act as ceRNAs for particular miRNAs to modulate the target genes of the miRNAs, including GC [ 43 , 44 ]. In this study, we assessed the subcellular localization of LINC01207 and observed that majority of LINC01207 were located in the cytoplasm of OSCC cells, which suggested that LINC01207 may function as a ceRNA for sponging miRNA.…”

Identification of vital prognostic genes related to tumor microenvironment in pheochromocytoma and paraganglioma based on weighted gene co-expression network analysis

“…Liu et al [ 22 ] reported for the first time that CCL18 was up-regulated in bladder cancer (BC) cells, which further promote cell migration, invasion and epithelial-mesenchymal transition (EMT). CCL18 overexpression has also been revealed to be associated with the proliferation, invasiveness, and angiogenesis of oral cancer cells, as well as the TNM stage [ 30 ]. However, there was no study investigating the role in PCPG.…”

Long Non-Coding RNA (lncRNA) in Oral Squamous Cell Carcinoma: Biological Function and Clinical Application

“…For example, when the lncRNA LEF1-AS1 was silenced, it caused the arrest of the G0/G1 cell cycle and suppressed cell proliferation and growth in vitro via inactivation of the Hippo signaling pathway [ 59 ]. Furthermore, some certain lncRNAs were verified to promote OSCC invasion, metastasis, and angiogenesis [ 62 , 103 ]. For example, MALAT-1 is closely related to the growth and metastasis of OSCC cells and through the regulation of target small proline-rich protein (SPRR) in order to promote distant metastasis [ 77 ].…”

“…For example, MALAT-1 is closely related to the growth and metastasis of OSCC cells and through the regulation of target small proline-rich protein (SPRR) in order to promote distant metastasis [ 77 ]. LINC00319 is downstream of Chemokine ligand 18 (CCL18), and overexpression of LINC00319 regulated the expression of VEGFA and MMP-9 to promote the angiogenic ability of OSCC cells [ 62 ]. Similarly, knockdown of FOXCUT led to the downregulation of angiogenesis factor VEGFA in Tca8113 and SCC9 cells, which indicated the potential function for FOXCUT in angiogenesis of OSCC [ 43 ].…”