miR‐125a is a microRNA that is frequently diminished in various human malignancies. However, the mechanism by which impaired miR‐125a promotes cancer growth remains undefined. In this study, we investigated the role of miR‐125a in the proliferation and apoptosis of multiple myeloma (MM). To do this, we used MM tissue samples (from 40 anonymous patients), normal matched control samples, and five MM‐derived cell lines. We also established a mouse model of MM xenograft to explore the effect of overexpression of miR‐125a on the MM growth in vivo. Quantitative real‐time polymerase chain reaction revealed that the miR‐125a expression was broadly reduced in MM tissues and cell lines. The impairment of miR‐125a in MM tissues was functionally relevant because the overexpression of miR‐125a remarkably decreased the cell viability and colony‐forming activity, at least in part, by promoting apoptosis in two miR‐125a‐deficient MM cell lines: NCI‐H929 and U266. Interestingly, we also discovered that the human gene encoding the ubiquitin‐specific peptidase 5 (USP5), which is known to promote cellular deubiquitination and ubiquitin/proteasome‐dependent proteolysis, was a direct transcriptional target for miR‐125a to repress. More importantly, the heterologous expression of USP5 significantly reversed the growth‐inhibitory effects of miR‐125a on MM cells in vitro. In the mouse xenograft model, overexpressed miR‐125a prominently inhibited the growth of MM tumors and concomitantly reduced the expression of USP5 in tumor tissues. These results suggest that miR‐125a inhibits the expression of USP5, thereby mitigating the proliferation and survival of malignant MM cells. We propose that USP5 acts as an oncoprotein in miR‐125a‐missing cancers.
Background This study aimed to investigate the correlation of long non‐coding RNA T‐cell factor 7 (lnc‐TCF7) with clinical features and prognosis in patients with multiple myeloma (MM). Methods Totally, 216 newly diagnosed symptomatic MM patients and 60 healthy controls (HCs) were enrolled. Bone marrow samples were collected from patients before treatment and from HCs on donation to detect lnc‐TCF7 expression in plasma cells by reverse transcription quantitative polymerase chain reaction. Besides, clinical response, progression‐free survival (PFS), and overall survival (OS) of patients were assessed. Results Lnc‐TCF7 expression was increased in patients with MM compared with HCs. Lnc‐TCF7 expression was highest in international staging system (ISS) stage III patients, followed by ISS stage II patients, and then ISS stage I patients, while lnc‐TCF7 expression was similar in patients with different immunoglobulin subtypes and Durie‐Salmon stages. Regarding chromosomal abnormalities, lnc‐TCF7 expression positively correlated with t(4; 14) and Del(17p), whereas no correlation of lnc‐TCF7 expression with t(14; 16), 1q21 amplification, Del(13q), or hyperdiploid was observed in patients with MM. Furthermore, lnc‐TCF7 expression positively correlated with serum creatinine, beta‐2‐microglobulin, and lactate dehydrogenase in patients. Besides, lnc‐TCF7 was negatively associated with complete response but not overall response rate in patients. Additionally, patients with lnc‐TCF7 high expression exhibited shorter PFS and OS compared to patients with lnc‐TCF7 low expression. Conclusion Lnc‐TCF7 might have clinical value in aiding disease management and prognosis prediction of MM.
Background Increasing evidences have revealed that solasodine, isolated from Solanum sisymbriifolium fruits, has multiple functions such as anti-oxidant, anti-tumor and anti-infection. However, its role in pancreatic cancer has not been well studied. Methods To explore the role of solasodine in pancreatic cancer, human pancreatic cell lines including SW1990 and PANC1 were treated with different concentrations of solasodine for 48 h, and cell viability was evaluated by MTT assay, cell invasion and migration were evaluated by Transwell assay. The effect of solasodine on the apoptosis of SW1990 and PANC1 cells was detected by flow cytometry. To further explore the antitumor effect of solasodine in vivo, an SW1990 tumor-bearing mouse model was constructed. The effects of solasodine on cytokines in the serum of SW1990 tumor-bearing mice were also evaluated by ELISA assay. Results Specifically, in vitro, solasodine could significantly inhibit the proliferation of pancreatic cancer cell lines SW1990 and PANC1 cells. Flow cytometric analysis indicated that solasodine could induce apoptosis of SW1990 and PANC1 cells. Western blot assay indicated that solasodine could significantly inhibit the activation of Cox-2/Akt/GSK3β signal pathway. Meanwhile, the release of Cytochrome c from mitochondria to cytoplasm which can raise the caspases cascade (C-caspase 3 and C-caspase 9) was significantly enhanced by solasodine. In vivo, the results showed that solasodine had potent anti-tumor activities with a lower cytotoxicity. In addition, the serum TNF-α, IL-2 and IFN-γ levels in SW1990 tumor-bearing mice after the treatment of solasodine was significantly increased. Conclusion Taken together, our results suggested that the solasodine could prevent the progression of pancreatic cancer by inhibiting proliferation and promoting apoptosis, as well as stimulating immunity, suggesting that solasodine might be a potential therapeutic strategy for pancreatic cancer.
Urate is a byproduct of purine metabolism, and elevated serum uric acid (SUA) levels (⩾7 mg/dl) can increase the risk of gout in humans. 1 Gout is caused by the formation and deposition of monosodium urate crystals and is the most common form of chronic inflammatory arthritis among men in addition to being a rising cause of arthritis in women. Global epidemiological studies indicate that gout incidence and prevalence are rising in both developed and developing countries. Elevated SUA and gout are also linked to a range of serious comorbidities including hypertension, obesity, diabetes, heart failure, and chronic kidney disease. 2,3 URAT1 (recombinant urate transporter 1) is a member of the organic anion transporter (OAT) family responsible for urate exchange in human proximal tubules, and its discovery was a key step in the clarification of the mechanistic basis for urate homeostasis. URAT1 is a 12-transmembrane domain protein that is primarily expressed within renal tissues along the apical brush border membrane of proximal
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