Nosip is a potential therapeutic target in hepatocellular carcinoma cells.

Nitric oxide synthase-interacting protein (Nosip) interacts with nitric oxide synthase (NOS) and regulates NO synthesis and release, which participates in various critical physiological and pathological processes. However, the role of Nosip in hepatocellular carcinoma (HCC) is unclear. In this study, Nosip expression was found to be elevated in HCC tissues and cells. Nosip siRNA transfection inhibited the proliferation and motility of HCC cells and promoted apoptosis. In contrast, overexpression of Nosip promoted proliferation and migration and invasion, and inhibited apoptosis of HCC cells. As a natural compound, quercetin exerted the effect of inhibiting the proliferation and motility of HCC cells, and this anticancer activity probably via repressing the expression of Nosip. Our results suggest that Nosip could act as an oncogene in the progression of HCC and that quercetin may be a potential natural compound for treating HCC by inhibiting the expression of Nosip.

Fbxo45 promotes the malignant development of esophageal squamous cell carcinoma by targeting GGNBP2 for ubiquitination and degradation.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers. Fbxo45, a substrate recognition subunit of E3 ligase, is critically involved in tumorigenesis and tumor progression. However, the function of Fbxo45 and the underlying mechanisms have not been elucidated in ESCC. We used cellular and molecular methods to explore the molecular basis of Fbxo45-mediated ESCC development. We found that ectopic overexpression of Fbxo45 promoted the growth of Kyse-150, Kyse30 and ECA-109 cells and inhibited the apoptosis. Moreover, overexpression of Fbxo45 promoted the migration and invasion of ESCC cells. Consistently, knockdown of Fbxo45 exhibited the opposite effects on ESCC cells. Mechanistically, we observed that Fbxo45 binds to GGNBP2 via its SPRY domain and targets GGNBP2 for ubiquitination and degradation. GGNBP2 overexpression exhibited anticancer activity in ESCC cells. Furthermore, Fbxo45 exerted its functions by regulating GGNBP2 stability in ESCC cells. Notably, overexpression of Fbxo45 facilitated tumor growth in mice. Strikingly, Fbxo45 was highly expressed in ESCC tissues, and GGNBP2 had a lower expression in ESCC specimens. High expression of Fbxo45 and low expression of GGNBP2 were associated with poor prognosis in ESCC patients. Fbxo45 was negatively correlated with GGNBP2 expression in ESCC tissues. Therefore, Fbxo45 serves as an oncoprotein to promote ESCC tumorigenesis by targeting the stability of the tumor suppressor GGNBP2 in ESCC.

The role of Fbxo5 in the development of human malignant tumors.

Fbxo5 (F-Box only protein 5), as a substrate recognition subunit of SCF (SKP1-Cullin1-Fbox) protein, plays a crucial role in various cellular processes through ubiquitination and degradation of multiple proteins. In recent years, many studies have pointed out that Fbxo5 is critically involved in carcinogenesis. Moreover, targeting Fbxo5 could have a therapeutic potential for cancer therapy. This review focuses on the functions of Fbxo5 in various types of human malignancies and its underlying molecular mechanisms. This review might lay the foundation for enhancing future investigation on Fbxo5 functions in cancer development and progression.

Nitidine chloride suppresses NEDD4 expression in lung cancer cells.

Nitidine chloride (NC) possesses anticancer properties in various types of human malignancies. However, the effects of NC on lung cancer cells have not been elucidated. Moreover, the molecular mechanism of NC-involved antitumor activity is unclear. Therefore, we aimed to determine the biological effect of NC and the underlying molecular insights in lung cancer cells. The antineoplastic function of NC was assessed by MTT assays, Annexin V-FITC/PI apoptosis assay, wound healing analysis, and Transwell chamber migration and invasion assay in lung cancer cells. NEDD4 modulation was evaluated by western blotting assays of lung cancer cells after NC treatments. NEDD4 overexpression and downregulation were employed to validate the critical role of NEDD4 in the NC-mediated tumor suppressive effects. We found that NC suppressed cell viability, migration and invasion, but induced apoptosis in lung cancer cells. Mechanistic exploration revealed that NC exhibited its antitumor effects by reducing NEDD4 expression. Furthermore, our rescue experiments dissected that overexpression of NEDD4 abrogated the NC-mediated antineoplastic effects in lung cancer cells. Consistently, downregulation of NEDD4 enhanced the NC-induced anticancer effects. Thus, NC is a promising antitumor agent in lung cancer, indicating that NC might have potential therapeutic applications in the treatment of lung cancer.

Primary testicular diffuse large B-cell lymphoma: Case series.

RATIONALE: Primary testicular lymphoma (PTL) is a rare type of extranodal non-Hodgkin's lymphoma (NHL). Although data of PTL in patients with diffuse large B-cell lymphoma (DLBCL) are accumulating, there are still patients respond poorly to prognosis. PATIENT CONCERNS: All patients had disease of the DLBCL subtype and those patients had primary involvement of the testis. In our studies, eleven patients had stage I/II disease, and 3 patients had advanced disease with B symptoms. Four patients exhibited a MYC+, BCL2+, and BCL6- expression pattern, 4 patients had a MYC+, BCL6+, and BCL2- expression pattern, and 3 patients had a MYC+, BCL2+, and BCL6+ expression pattern. Additionally, 43% (7/16) of PT-DLBCL patients had a germinal center B-cell-like (GCB) phenotype, while the others had a non-GCB phonotype. DIAGNOSES: In our case, most patients presented with unilateral painless scrotal swelling and the enlargement of the testicles in the first examination. After hospitalization, all patients underwent preoperative imageological examination of the testis and epididymis and postoperative revealed that all patients were the diffuse infiltration of a large number of anomalous lymphocytes. In addition, no invasion of other sites was observed within 3 months after diagnosis. INTERVENTIONS AND OUTCOMES: Underwent orchiectomy on the affected side was performed by urologists after all patients were diagnosed with PTL. Meanwhile, some patients received at least one course of chemotherapy, or received postoperative combined RT and chemotherapy. Because of it particularity, nineteen instances of lymph node region involvement were discovered in 12 patients since the operation. LESSONS: PT-DLBCL has unique biological characteristics, and its treatment modalities are becoming increasingly standardized. In the future, systematic interventions need to be actively considered in the early stages of PTL.

Antitumor functions and mechanisms of nitidine chloride in human cancers.

Nitidine chloride (NC), a quaternary ammonium alkaloid, exhibits multiple biological activities, including antimalarial, antifungal, and antiangiogenesis. Recently, NC has been characterized to perform antitumor activity in a variety of malignancies. NC has been identified to suppress cell proliferation, stimulate apoptosis, and induce cell cycle arrest, retard migration, invasion and metastasis. Moreover, NC is reported to sensitize cancer cells to chemotherapeutic drugs. In this review article, we describe the functions of NC in human cancers and discuss the molecular insight into NC-involved antitumor feature. This review article will stimulate the deeper investigation for using NC as a potent agent for the management of cancer patients.