The long noncoding RNA X-inactive specific transcript (XIST) plays vital roles in tumor progression. However, the underlying mechanisms remain unclear. This study investigated the effects and mechanisms of targeting XIST on osteosarcoma (OS) cells in vitro and in vivo. We used shRNA to knockdown XIST to evaluate cell growth and apoptosis in U2OS cells in vitro and xenograft formation in vivo. An observed relationship between XIST and the p53 upregulated modulator of apoptosis (PUMA) and nuclear factor-kappa B (NF-kB) pathway was further explored by using small interfering RNA (siRNA). Our results showed that suppression of XIST by short hairpin RNA (shRNA) impeded U2OS cell growth, induced apoptosis and lessened OS xenograft tumor growth. Targeting XIST increased NF-kB-dependent PUMA upregulation in U2OS cells. Upregulation of PUMA is correlated with suppression of XIST-induced apoptosis in U2OS cells. Therefore, inhibition of XIST could promote U2OS cell death via activation of NF-kB/PUMA pathways.

Osteosarcoma (OS) is the most common primary malignant bone tumor. Secretory apolipoprotein J/clusterin (sCLU) is overexpressed in many cancers; however, its role in OS has not been previously investigated. The objectives of this study were to address this question and also to assess the clinical value of sCLU as a prognostic biomarker and therapeutic target by comparing sCLU expression in human OS (n = 106), normal bone (n = 16), fibrous dysplasia (n = 9), and ossifying myositis (n = 11) tissues and by evaluating the effect of sCLU silencing on OS growth, invasion, and chemosensitivity in vitro and in vivo. We found that sCLU was highly expressed in OS tissue specimens, which was positively correlated with metastatic disease and negatively correlated with response to chemotherapy. sCLU knockdown in KHOS cells inhibited proliferation and invasion and increased apoptosis as well as sensitivity to the chemotherapy drug gemcitabine (Gem). In a mouse xenograft model, sCLU depletion suppressed lung metastasis and enhanced the effects of Gem, thereby slowing KHOS tumor growth. These results indicate that sCLU overexpression is a biomarker for malignant transformation of OS and that therapeutic strategies targeting sCLU may be an effective treatment for OS. Highlights• Secretory apolipoprotein J/clusterin (sCLU) is overexpressed in osteosarcoma (OS).• sCLU overexpression is associated with metastasis and chemoresistance.• Silencing sCLU inhibits metastasis and enhances chemosensitivity in OS cells. sCLU is a biomarker for metastatic OS and a potential therapeutic target. ARTICLE HISTORY

The multifarious assortment of microorganisms present in gut of humans is termed as gut microbiota. These include 1,000 species accompanied by approximately 2 million genes in an individual adult. The gut microbiota has multifactorial protective roles against allergic reactions, inflammation, cardiac pathological states and even in the state of malignant carcinogenesis existing in humans. By contrast, adverse alterations in the microbiota result in chronic pathological states, including autoimmune diseases, cancer and circulatory system obstructions. Gut bacteria also maintain sensitivity towards nutritional changes as well as antibiotics. The present review article focused on the importance of gut bacteria in newborn infants with special reference to their protective role in various pediatric pathological states linked with gut bacteria. In addition, the importance of probiotics in relation to gut microbiota are to be discussed.