Alkannin restrains oral squamous carcinoma cell growth, migration and invasion by regulating microRNA-9/RECK axis

Abstract

Alkannin (ALK) has anti-inflammatory and anti-tumour activities. We tried to probe the underlying functions of ALK in oral squamous carcinoma (OSCC) cells growth, migration and invasion. OSCC cells viability was investigated after treatment with ALK. Then, BrdU, flow cytometry, Western blot and Transwell assays were executed to appraise proliferation, apoptosis, migration and invasion in OSCC cells with ALK stimulation. The biological functions of miR-9 were explored after miR-9 mimic/inhibitor transfection. The relevance of RECK and miR-9 was predicated by dual luciferase activity assay. JAK1/ STAT3 and PI3K/AKT pathways were estimated by Western blot. Tumour formation in vivo was executed by xenograft tumours assay. We found that ALK restrained cell proliferation, facilitated apoptosis, repressed migration and invasion also interdicted JAK1/STAT3 and PI3K/AKT pathways in CAL-27 and SCC-9 cells. miR-9 expression was upgraded in OSCC tissues but decreased in OSCC cells along with ALK administration; meanwhile, overexpressed miR-9 inverted the influences of ALK in OSCC cells growth, migration and invasion. RECK was predicated as a novel target gene of miR-9, and overexpressed RECK hindered JAK1/STAT3 and PI3K/AKT pathways in OSCC cells. ALK prohibited tumour formation in vivo. In conclusion, ALK restrained OSCC cells growth, migration and invasion via adjusting miR-9/RECK axis. HIGHLIGHTS 1. ALK restrains cell growth, migration and invasion in OSCC cells; 2. miR-9 is enhanced in OSCC tissues but is repressed by ALK in OSCC cells; 3. miR-9 inverts the repressive effect of ALK on CAL-27 and SCC-9 cells; 4. RECK is a novel target of miR-9; 5. ALK or RECK hinders JAK1/STAT3 and PI3K/AKT pathways in CAL-27 and SCC-9 cells; 6. ALK prohibits tumour formation in vivo. ARTICLE HISTORY

Alkannin exerts antitumor properties in cutaneous squamous cell carcinoma by inducing apoptosis and shifting the M1/M2 polarization of tumor‐associated macrophages by upregulating PTEN

“…In this work, we discovered that alkannin restricted CSCC cell viability in a dose‐dependent manner and accelerated CSCC cell apoptosis. This result was similar to the description of Mao et al 23 In addition, Nika et al indicated that polarization of macrophages served as a key regulatory factor in CSCC 24 . Moreover, Marie et al proved that oncostatin M is involved in modulating cell proliferation, migration, and macrophage M1 polarization to promote CSCC development 25 .…”

“…Earlier studies have shown that alkannin plays a central role in many cancers. Mao et al showed that alkannin hindered oral squamous carcinoma cell growth, migration, and invasion while expediting apoptosis by modulating the miR‐9/RECK axis 23 . In this work, we discovered that alkannin restricted CSCC cell viability in a dose‐dependent manner and accelerated CSCC cell apoptosis.…”

Retracted: Alkannin represses growth of pancreatic cancer cells based on the down regulation of miR‐199a

“…To reveal the fundamental role of alkannin in cellular activities, we ascertained the treatment time and R e t r a c t e d concentrations of alkannin which was evaluated by detecting cell viability. According to a previous reported treatment time, 24 we incubated PANC-1 cells with 0, 1, 3, 5, and 10 μM of alkannin for 12 hr. Results in Figure 1b suggested that the viability was significantly repressed by alkannin at concentrations of 3 (p < .05), 5 (p < .01), and 10 μM (p < .001).…”

microRNA 21 Promotes the Proliferation and Metastasis of Oral Squamous Cell Carcinoma by Targeting RECK

“…A previous study demonstrated the regulatory mechanism underlying the targeting of RECK by miR-21 in other cancers; this study revealed that the molecular mechanisms underlying the promotion of cell proliferation, viability, invasion, and apoptosis by miR-21 via its target gene, i.e., RECK, are common in Gejiu squamous cell lung carcinoma and other non-small cell lung carcinomas 14) . In contrast, RECK inhibits tumor cell proliferation, invasion, and angiogenesis in several cancers, including OSCC [15][16][17][18] .…”