<p>Long Non-Coding RNA ASB16-AS1 Functions as a miR-760 Sponge to Facilitate the Malignant Phenotype of Osteosarcoma by Increasing HDGF Expression</p>

Abstract

Purpose: ASB16 antisense RNA 1 (ASB16-AS1) is a cancer-associated long non-coding RNA that contributes to tumorigenesis and tumor development. Nevertheless, to the best of our knowledge, whether and how ASB16-AS1 is implicated in osteosarcoma (OS) malignancy remains unclear and therefore warrants exploration. Our current study focused on making in-depth investigation of ASB16-AS1 in OS. In the present study, the expression pattern of ASB16-AS1 in OS tissues and cell lines was analyzed. In addition, we examined the clinical value of ASB16-AS1 for OS patients. Furthermore, we explored the impacts of ASB16-AS1 on the malignant phenotype of OS cells in vitro and in vivo as well as the underlying mechanism. Methods: ASB16-AS1, microRNA-760 (miR-760) and hepatoma-derived growth factor (HDGF) expressions were measured using reverse transcription-quantitative PCR. Cell proliferation and apoptosis were evaluated using CCK-8 and flow cytometry analyses, respectively, and cell migration and invasion were determined via cell migration and invasion assays. Results: ASB16-AS1 expression was significantly elevated in OS tissues and cell lines, and increased ASB16-AS1 expression was related to patients' tumor size, TNM stage, and distant metastasis. The overall survival rate of OS patients presenting high ASB16-AS1 expression was shorter than that of patients presenting low ASB16-AS1 expression. Reduced ASB16-AS1 expression inhibited OS cell proliferation, migration, and invasion; promoted cell apoptosis; and impaired tumor growth in vivo. Mechanistically, ASB16-AS1 served as a sponge for miR-760 and positively modulated the expression of its target HDGF. Finally, inhibiting miR-760 and restoring HDGF expression abolished the impacts of ASB16-AS1 knockdown on the malignant characteristics of OS cells. Conclusion: ASB16-AS1 is a novel oncogenic lncRNA in OS cells. ASB16-AS1 increased HDGF expression by sponging miR-760, thereby conferring cancer-promoting roles in OS. ASB16-AS1 is a potential early diagnostic and therapeutic target in OS.

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies

“…The fact that HDGF is a representative member of a gene family ( Figure 1; Figure 2) might be advantageous when we consider it as a therapeutic target. Recently, the significant roles of HDGF in malignant diseases were reported for many non-digestive malignant diseases, including osteosarcoma [61,62], endometrial cancer [63,64], lung cancer [65][66][67], malignant glioma [68][69][70], cervical cancer [71], ovarian cancer [72] and breast cancer [73]. Thus, HDGF is considered as a potential target molecule for anticancer therapy.…”

“…Recently, non-coding RNAs, such as microRNAs and long non-coding RNAs (lncRNAs), which modulate the function of the target genes, have been shown to have an important role in several diseases [77,78]. Indeed, various microRNAs [40,61,62,[64][65][66][67]69,72] and lncRNAs [49,61,69,71,73] have been suggested to be involved in the regulation of the functions of HDGF, findings that may support the development of HDGF-targeting therapies. For instance, lncRNA HLA complex P5 (lnc HCP5) was reported to cause gemcitabine resistance in pancreatic cancer cells, through the upregulation of miR-214-3p and its target gene, HDGF [40].…”

miR-140 inhibits osteosarcoma progression by impairing USP22-mediated LSD1 stabilization and promoting p21 expression

“…The inhibition of proliferation, migration, and invasion, along with increased apoptosis in osteosarcoma cells, was associated with impaired tumor growth in vivo . 27 Taken above, we proposed that overexpression of miR-140 impaired tumor growth of osteosarcoma by suppressing osteosarcoma cell migration, invasion, and promoting apoptosis.…”

Long noncoding RNA ASB16-AS1 inhibits adrenocortical carcinoma cell growth by promoting ubiquitination of RNA-binding protein HuR

“…Studies have found that ASB16-AS1 promotes cell proliferation in glioma, hepatocellular carcinoma, cervical cancer, non-small cell lung cancer and in osteosarcoma [17][18][19][20][21] . However, the biological function and molecular mechanism of ASB16-AS1 in adrenocortical carcinoma remains unknown.…”

“…Studies found that E3 ligase β-TrCP1 (BTRC) target HuR for ubiquitin-mediated protein degradation 14,16 . Several studies have found that ASB16-AS1 regulate proliferation in glioma, hepatocellular carcinoma, cervical cancer, non-small cell lung cancer, and in osteosarcoma [17][18][19][20][21] . However, whether ASB16-AS1 plays an important role in adrenocortical carcinoma remains to be clarified.…”