Long noncoding RNA HOXA-AS2 promotes non-small cell lung cancer progression by regulating miR-520a-3p

Abstract

Background: The HOXA cluster antisense RNA 2 (HOXA-AS2) has recently been discovered to be involved in carcinogenesis in multiple cancers. However, the role and underlying mechanism of HOXA-AS2 in non-small cell lung cancer (NSCLC) yet need to be unraveled. Methods: HOXA-AS2 expression in NSCLC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). Furthermore, the effects of HOXA-AS2 on NSCLC cell proliferation, apoptosis, migration, and invasion were assessed by MTS, flow cytometry, wound healing and transwell invasion assays, respectively. Starbase2.0 predicted and luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the association of HOXA-AS2 and miR-520a-3p in NSCLC cells. Results: Our results revealed that HOXA-AS2 in NSCLC tissues were up-regulated and cell lines, and were associated with poor prognosis and overall survival. Further functional assays demonstrated that HOXA-AS2 knockdown significantly inhibited NSCLC cell proliferation, induced cell apoptosis and suppressed migration and invasion. Starbase2.0 predicted that HOXA-AS2 sponge miR-520a-3p at 3′-UTR, which was confirmed using luciferase reporter and RIP assays. miR-520a-3p expression was inversely correlated with HOXA-AS2 expression in NSCLC tissues. In addition, miR-520a-3p inhibitor attenuated the inhibitory effect of HOXD-AS2-depletion on cell proliferation, migration and invasion of NSCLC cells. Moreover, HOXA-AS2 could regulate HOXD8 and MAP3K2 expression, two known targets of miR-520a-3p in NSCLC. Conclusion: These findings implied that HOXA-AS2 promoted NSCLC progression by regulating miR-520a-3p, suggesting that HOXA-AS2 could serve as a therapeutic target for NSCLC.

LncRNA HOXA-AS2 promotes glioblastoma carcinogenesis by targeting miR-885-5p/RBBP4 axis

“…For instance, in one study, HOXA-AS2 stimulated the proliferation, migration and invasion of osteosarcoma cells [11]. Several studies described HOXA-AS2 as an oncogene that promoted the malignant proliferation of non-small cell lung cancer cells [33][34][35]. Similarly, HOXA-AS2 was demonstrated in another research to advance bladder cancer cells by directly regulating the expression of miR-125b [36].…”

Long non-coding RNA HOXA-AS2 may serve as a new therapeutic target and promising prognostic market for most of cancers

“…In the end, 12 articles with a total of 796 patients (Table 1) were included in this study. There were 8 types of cancer in these 12 literatures, including 2 cases of lung cancer [17,18], 2 of thyroid cancer [19,20], 1 of bladder cancer [21], 1 of breast cancer [22], 1 of gastric cancer [23], 2 of colorectal cancer [9,10], 1 of osteosarcoma [24] and 2 cases of liver cancer [14,25]. All the 12 articles come from China (Table 1).…”

“…At present, studies have confirmed that long-chain non-coding RNAHOXA-AS2 can take part in the progression of AML, thyroid papillary carcinoma, HCC and breast cancer throuh target regulating of miR-520c-3p [12,14,19,22]. In addition, HOXA-AS2 can promote the malignant progression of non-small cell lung cancer, thyroid papillary carcinoma and liver cancer through miRNA-216a-5p, miR-520a-3p, miR-15a-5p and miR-125b [17,18,20,21]. And the KEGG showed that HOXA-AS2 was associated with cancer, MAPK pathway, NOD receptor pathway and Ca ion signaling pathway.…”

HOXA-AS2 Promotes Glioblastoma Carcinogenesis by Targeting miR-885-5p Thus Releasing RBBP4 mRNA

“…For instance, HOXA-AS2 has been shown to stimulate osteosarcoma cell proliferation, migration and invasion [11]. Several studies described HOXA-AS2 as an oncogene that promoted the malignant proliferation of non-small cell lung cancer cells [24][25][26]. Similarly, HOXA-AS2 was indicated to advance bladder cancer by directly regulating the expression of miR-125b, thereby regulating Smad2 [27].…”