LncRNA HOXC-AS3 overexpression inhibits TGF-β2-induced colorectal cancer cell migration and invasion by sponging miR-1269

Abstract

Objective Long non-coding RNA (lncRNA) HOXC-AS3 has been characterized as a cancer-related lncRNA in many types of cancer, while its role in colorectal cancer (CRC) is unknown. Methods The expression of HOXC-AS3 and TGF-β2 were detected by RT-qPCR. Overexpression assays were performed to explore the interaction between HOXC-AS3 and TGF-β2. A follow-up study was performed to explore the prognostic value of HOXC-AS3 for CRC. The direct interaction between HOXC-AS3 and miR-1269 was assessed with RNA-RNA pulldown assay. Transwell assays were performed to determine the role of HOXC-AS3 and TGF-β2 in regulating CRC cell invasion and migration. Results HOXC-AS3 was significantly downregulated in CRC tissues, while TGF-β2 was significantly upregulated in CRC tissues compared to that in adjacent non-cancer tissues of CRC patients. The follow-up study showed that low expression levels of HOXC-AS3 in CRC tissues were closely correlated with poor survival. Correlation analysis showed that HOXC-AS3 and TGF-β2 were inversely correlated across CRC tissues but not non-cancer tissues. Overexpression of HOXC-AS3 in the two cell lines resulted in downregulation of TGF-β2, while the expression of HOXC-AS3 was not affected by TGF-β2. Transwell migration and invasion assay showed that overexpression of TGF-β2 increased cell invasion and migration, while overexpression of HOXC-AS3 decreased cell migration and invasion. In addition, overexpression of HOXC-AS3 attenuated the effects of overexpression of TGF-β2. MiR-1269 increased the expression of TGF-β2. HOXC-AS3 directly interacted with miR-1269 in CRC cells. Conclusions Upregulation of HOXC-AS3 inhibited TGF-β2-induced colorectal cancer (CRC) cell migration and invasion possibly by sponging miR-1269.

HOXC Cluster Antisense RNA 3, a Novel Long Non-Coding RNA as an Oncological Biomarker and Therapeutic Target in Human Malignancies

“…Interestingly, HOXC‑AS3 was significantly positively correlated with the well-known oncogenic lncRNA HOTAIR, but negatively correlated with HOXC10. 37 In a subsequent study by Zhang et al, 12 HOXC-AS3 was reported to be significantly downregulated in CRC tissues and CRC cell lines. The observed differences in HOXC-AS3 expression in CRC tissues may be attributed to the ethnicity of the individuals in these two studies.…”

“…The observed differences in HOXC-AS3 expression in CRC tissues may be attributed to the ethnicity of the individuals in these two studies. Zhang et al 12 also found that low HOXC-AS3 levels were indicative of poor survival in CRC patients. Notably, HOXC-AS3 overexpression effectively impedes TGF-β2-induced migration and invasion in CR4 and RKO colorectal cancer cells by acting as a sponge for miR-1269.…”

“…Notably, HOXC-AS3 overexpression effectively impedes TGF-β2-induced migration and invasion in CR4 and RKO colorectal cancer cells by acting as a sponge for miR-1269. 12 This is of significance as a positive feedback loop between TGF-β signaling and miR-1269 has been reported to promote metastasis in colorectal cancer. 50 …”

“…HOXC-AS3 displayed different prognostic significance in different cancer types. In most of the reported tumors, including gastric cancer, 17 glioma, 16 breast cancer, 11 , 19 , 20 cervical cancer, 36 hepatocellular carcinoma, 15 HOXC-AS3 overexpression tends to predict poor prognosis, whereas in colorectal cancer (CRC), 12 high expression of HOXC-AS3 indicates good prognosis.…”

“…Several studies have shown HOXC‑AS3 could functions as a ceRNA by interacting with miRNAs, including miR-216 in glioma, 16 miR-3922-5p 20 and miR-1224-5p in breast cancer, 11 miR-105-5p in cervical cancer, 36 miR-1269 in colorectal cancer. 12 Additionally, several assays, including luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down, have identified miRNA binding sites on HOXC-AS3. Functional assays demonstrated that miRNAs and their target mRNAs regulate HOXC-AS3’s effects.…”