Circ‐HOMER1 enhances the inhibition of miR‐1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide accompanying with the high rate of recurrence. Accumulating reports have documented the significance of circular RNAs (circRNAs) in carcinogenesis and development of HCC. This study aimed to establish the mechanism underlying circ‐HOMER1 involvement in HCC. To this end, we identified a binding site for miR‐1322 via bioinformatics, quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR), and dual‐luciferase reporter assays providing evidence of a direct link between circ‐HOMER1 and miR‐1322. Similarly, the target gene of miR‐1322 was investigated. Moreover, we determined the specific function of circ‐HOMER1 in HCC with the aid of qRT‐PCR based on patient clinical records, Cell Counting Kit‐8, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, and wound‐healing and transwell assays. Notably, circ‐HOMER1 was upregulated in both HCC cells and tissues. This aberrant expression pattern was closely correlated with larger tumor size, higher tumor‐node‐metastasis stage, and poorer prognosis for the patients with HCC. Moreover, silenced circ‐HOMER1 inhibited cell proliferation, migration, and invasion concomitant with the promotion of apoptosis in HCC cells, and vice versa. Mechanistically, circ‐HOMER1 enhanced the inhibition of miR‐1322 on CXCL6 in HCC. Furthermore, we found that circ‐HOMER1 promoted HCC cell growth and aggressiveness by miR‐1322/CXCL6 axis. This study may provide a potential prognostic indicator and therapeutic target for patients with HCC.

<p>Hsa_circ_0006916 Knockdown Represses the Development of Hepatocellular Carcinoma via Modulating miR-599/SRSF2 Axis</p>

“…30 A previous study suggested that circ_0006916 played an important role in HCC development. 15 In this study, we found that circ_0006916 could repress HCC development. Moreover, we were the first time to validate it was associated with circ_0006916/miR-599/SRSF2 network in HCC.…”

“…In this research, we found circ_0006916 abundance was elevated in HCC, which was also consistent with former reports. 14,15 Moreover, by treatment of RNase R and Actinomycin D, we found that circ_0006916 was stably expressed in HCC cells. To explore the potential role of circ_0006916, we performed the loss-of-function experiments, and found that circ_0006916 interference restrained HCC development via reducing cell viability, colony ability, migration and invasion and increasing cycle arrest and apoptosis, which was also like that in a previous report.…”

“…14 Furthermore, circ_0006916 can promote HCC cell proliferation, migration and invasion via modulating miR-1322/C-X-C motif chemokine ligand 6 (CXCL6) axis. 15 Nevertheless, the mechanism addressed by circ_0006916 is complex, and additional regulatory network of circ_0006916 is expected to be explored.…”

Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization

“… 40 In addition, Circ-HOMER1 enhances the inhibition of miR-1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma. 41 We used a public prediction database to confirm that miR-1322 directly regulated CCL20 expression. Our results showed that the expression of miR-1322 was decreased in CRC patients, and F. nucleatum regulated the expression of CCL20 via miR-1322.…”

The Roles of circRNAs in Liver Cancer Immunity

“…On the contrary, hsa_circ_0003645 promoted cell migration, invasion and suppressed cell apoptosis ( 157 ). Circ-HOMER1 enhanced the proliferation, migration, invasion, and suppressed apoptosis ( 158 ). In addition, exosomal hsa_circ_0051443 enhanced cell apoptosis ( 159 ).…”