LINC00173.v1 promotes angiogenesis and progression of lung squamous cell carcinoma by sponging miR-511-5p to regulate VEGFA expression

Abstract

Background Anti-angiogenic therapy represents a promising strategy for non-small-cell lung cancer (NSCLC) but its application in lung squamous cell carcinoma (SQC) is limited due to the high-risk adverse effects. Accumulating evidence indicates that long noncoding RNAs (lncRNAs) mediate in tumor progression by participating in the regulation of VEGF in NSCLC, which might guide the development of new antiangiogenic strategies. Methods Differential lncRNA expression in SQC was analyzed in AE-meta and TCGA datasets, and further confirmed in lung cancer tissues and adjacent normal tissues with RT-qPCR and in-situ hybridization. Statistical analysis was performed to evaluate the clinical correlation between LINC00173.v1 expression and survival characteristics. A tube formation assay, chick embryo chorioallantoic membrane assay and animal experiments were conducted to detect the effect of LINC00173.v1 on the proliferation and migration of vascular endothelial cells and tumorigenesis of SQC in vivo. Bioinformatics analysis, RNA immunoprecipitation and luciferase reporter assays were performed to elucidate the downstream target of LINC00173.v1. The therapeutic efficacy of antisense oligonucleotide (ASO) against LINC00173.v1 was further investigated in vivo. Chromatin immunoprecipitation and high throughput data processing and visualization were performed to identify the cause of LINC00173.v1 overexpression in SQC. Results LINC00173.v1 was specifically upregulated in SQC tissues, which predicted poorer overall and progression-free survival in SQC patients. Overexpression of LINC00173.v1 promoted, while silencing LINC00173.v1 inhibited the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC cells in vitro and in vivo. Our results further revealed that LINC00173.v1 promoted the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC cells by upregulating VEGFA expression by sponging miR-511-5p. Importantly, inhibition of LINC00173.v1 via the ASO strategy reduced the tumor growth of SQC cells, and enhanced the therapeutic sensitivity of SQC cells to cisplatin in vivo. Moreover, our results showed that squamous cell carcinoma-specific factor ΔNp63α contributed to LINC00173.v1 overexpression in SQC. Conclusion Our findings clarify the underlying mechanism by which LINC00173.v1 promotes the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC, demonstrating that LINC00173.v1-targeted drug in combination with cisplatin may serve as a rational regimen against SQC.

SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

“…VEGFA (Vascular endothelial growth factor-A) is a primary factor driving expansion of the tumor vascular bed [25]. VEGFA is involved in the regulation of various tumor angiogenesis (such as lung squamous cell carcinoma [26], ovarian cancer [27], etc.). MMP2 and VEGFA are both recognized as the molecular biomarkers of tumor angiogenesis.…”

LINC01128 regulates the development of osteosarcoma by sponging miR‐299‐3p to mediate MMP2 expression and activating Wnt/β‐catenin signalling pathway

“…Long non‐coding RNAs (lncRNAs) are a type of RNA with lengths exceeding 200 nucleotides that do not encode proteins 11 . LncRNAs have attracted increasing attention as cancer biomarkers for early screening, diagnosis, prognosis and response to drug treatment 12‐14 . Although several lncRNAs including lncRNA ODRUL, 11,15 SNHG15, 16 SNHG16, 17 SNHG4 18 and AFAP1‐AS 19 have been confirmed to be highly correlated with OS, no widely applicable therapeutic targets have not been identified thus far.…”

Comprehensive evaluation of differential long non‑coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra

“…Some lncRNAs can serve as competitive endogenous RNAs (ceRNAs) of microRNA (miRNA/miR) to modulate the downregulation of miRNA targets (11). The functions of lncRNAs in cancer and several other diseases have been investigated (12)(13)(14)(15). For instance, Chen et al (12) reported that LINC00173.v1 upregulated the expression of VEGFA via sponging miR-511-5p to promote the proliferation and migration of vascular endothelial cells.…”

“…The functions of lncRNAs in cancer and several other diseases have been investigated (12)(13)(14)(15). For instance, Chen et al (12) reported that LINC00173.v1 upregulated the expression of VEGFA via sponging miR-511-5p to promote the proliferation and migration of vascular endothelial cells. Wang et al (13) also revealed that CARL lncRNA inhibited mitochondrial fission and apoptosis by upregulating prohibitin 2 expression via decreasing the expression of miR-539.…”