Schisandrin B Inhibits Cell Viability and Migration, and Induces Cell Apoptosis by circ_0009112/miR-708-5p Axis Through PI3K/AKT Pathway in Osteosarcoma

Abstract

Osteosarcoma is a primary tumor of bone and its incidence is increasing. Schisandrin B (Sch B), a generally used lignan in Chinese medicine, has been found to repress cancer progression. This study aims to reveal the effects and regulatory mechanism of Sch B in the viability, apoptosis and migration of osteosarcoma cells. In this study, we found circ_0009112 expression was higher and miR-708-5p expression was lower in SaOS2 and U2OS cells than in hFOB1.19 cells. Circ_0009112 expression was downregulated, but miR-708-5p was upregulated by Sch B treatment in a dose-dependent manner in SaOS2 and U2OS cells. Sch B exposure inhibited osteosarcoma development in vitro and in vivo; however, these effects were restored by circ_0009112. Furthermore, circ_0009112 acted as a sponge of miR-708-5p. Circ_0009112 regulated PI3K/AKT pathway after Sch B treatment by associating with miR-708-5p. Sch B exposure inhibited cell viability and migration, whereas promoted cell apoptosis by regulating circ_0009112/miR-708-5p axis through PI3K/AKT pathway in osteosarcoma cells. This study provided a theoretical basis for further studying osteosarcoma therapy with Sch B.

MiR‐708‐5p/Pit‐1 axis mediates high phosphate‐induced calcification in vascular smooth muscle cells via Wnt8b/β‐catenin pathway

“…MiRNAs are short noncoding RNAs that bind to their 3 0 /5 0untranslated regions at the post-transcriptional level to regulate gene expression. 24 Studies have shown that miRNAs play an important role in gene expression by regulating post-transcriptional translation, which may be involved in the regulation of a variety of disease progression. 6 Without exception, studies have reported that miR-708-5p plays an important role in a variety of physiological and pathological processes.…”

The Double Face of miR-708: A Pan-Cancer Player with Dissociative Identity Disorder

“…Such molecules sequester miRNAs in a complex regulatory network in which RNAs can regulate each other by competing for a limited pool of miRNAs [ 50 ]. In this regard, many long non-coding RNAs have been included in these ceRNA networks, including NONRATT009773.2/miR-708-5p/CXCL13 in bone cancer [ 51 ]; LINC00514/miR-708-5p/HOXB3 in cervical squamous cell carcinoma [ 52 ]; LINC00665/miR-708 and miR-142-5p/RAP1B in osteosarcoma [ 53 ]; Meg3/miR-708/SOCS3 in colorectal cancer [ 54 ]; LOXL1-AS1/miR-708-5p/USF1 and NF-κB [ 55 , 56 ]; and the RNAs circ_0009112 and MINCR, sponging miR-708-5p and regulating PI3K/AKT and Wnt/β-catenin pathways [ 57 , 58 ].…”

Schisandrin B Suppresses Colon Cancer Growth by Inducing Cell Cycle Arrest and Apoptosis: Molecular Mechanism and Therapeutic Potential

“…8 So far, there are a number of studies published exploring the effect of polyphenols on colorectal cell lines or animal models. 9−11 Schisandrin B (Sch B), a lignan extracted from the fruit of Schisandra chinensis, has been reported for its anticancer properties in various cancers, for example, liver cancer, 12 breast cancer, 13,14 ovarian cancer, 15 glioma, 16 osteosarcoma, 17 and gastric cancer. 18,19 More recently, studies have shown that Sch B was able to prevent or treat colitis-associated colon cancer.…”

“…Schisandrin B (Sch B), a lignan extracted from the fruit of Schisandra chinensis, has been reported for its anticancer properties in various cancers, for example, liver cancer, breast cancer, , ovarian cancer, glioma, osteosarcoma, and gastric cancer. , More recently, studies have shown that Sch B was able to prevent or treat colitis-associated colon cancer. , Although the antitumor activities of Sch B have been confirmed in various cancer types, the potential mechanism of Sch B seems much more complex, ranging from cell cycle arrest to programmed cell death. For example, in liver cancer, Sch B induced G0/G1 cell cycle arrest and apoptosis by upregulating caspase-3 and Bcl-2 family members in cholangiocarcinoma (CCA), and reduced tumor growth in a xenograft mouse model .…”

“…In another study by Li et al, Sch B was shown to induce glioma cell apoptosis by diminishing the mitochondrial membrane potential (ΔΨm). Other studies have also reported that Sch B induces apoptosis and cell cycle arrest via Wnt/β-catenin, PI3K/AKT, , NF-κB, and p38 MAPK signaling pathways . However, none of these studies have fully characterized the mechanism of the antitumorigenic effect of Sch B, especially in colon cancer.…”