Lentivirus-mediated down-regulation of CK2α inhibits proliferation and induces apoptosis of malignant lymphoma and leukemia cells.

Casein kinase II subunit alpha (CK2α) is highly expressed in many malignant tumor tissues, including lymphomas and leukemia. To investigate the role of CK2α in cell proliferation and apoptosis of malignant lymphomas and leukemia, 2 lymphoma cell lines and one leukemia cell line were infected with CK2α shRNA lentivirus or negative control shRNA lentivirus, and stably infected cell lines were established. Real-time PCR and Western blot results showed that the mRNA and protein levels of CK2α were significantly reduced in CK2α knockdown cells. The tetrazolium-based colorimetric (MTT) assay found that down-regulation of CK2α inhibited the proliferation of these cells. Flow cytometry analysis showed that inhibition of CK2α induced cell cycle arrest and apoptosis of lymphoma and leukemia cells. In accordance with these, down-regulation of CK2α also reduced the protein levels of proliferating cell nuclear antigen (PCNA), cyclinD1, and bcl-2, and increased the protein expression of bax, cleaved caspase-3, cleaved caspase-9, and cleaved poly(ADP ribose) polymerase (PARP). Moreover, knockdown of CK2α impeded the growth of xenograft tumors in vivo. In summary, our study revealed that CK2α may contribute to the development of malignant lymphoma and leukemia, and serve as the therapeutic target of these malignant tumors.

Enhanced antitumor effect of combination of annexin A1 knockdown and bortezomib treatment in multiple myeloma in vitro and in vivo.

Bortezomib (BTZ) is one of the most frequently used drugs in treatment of multiple myeloma (MM), but drug-resistance often occurs and limits its clinical efficacy. Annexin A1 (ANXA1) is upregulated in MM, and its knockdown enhances chemosensitivity in MM. However, whether ANXA1 inhibition can increase antitumor activity of BTZ in MM cells remains unknown. In the present study, Cell Counting Kit-8 (CCK-8) and colony formation assays showed that ANXA1 silencing combined with BTZ treatment led to a more significant inhibition of MM cell proliferation than each treatment alone. Cell apoptosis was dramatically promoted in MM cells following silencing of ANXA1 and BTZ administration versus that in ANXA1-silenced alone or BTZ-treated alone cells, as evidenced by decreased expression of phosphorylated signal transducers and activators of transcription 3 and BCL2, and increased expression of BAX. Moreover, we demonstrated that the levels of IL-6 and IL-23 were markedly downregulated in ANXA1-silenced and BTZ-treated MM cells. Furthermore, the combination of ANXA1 knockdown and BTZ treatment distinctly suppressed tumor growth in vivo compared with BTZ treatment alone. Taken together, our results show that downregulation of ANXA1 enhances antitumor activity of BTZ in MM in vitro and in vivo, indicating that ANXA1 may be a promising target for enhancing the chemosensitivity of MM to BTZ.

Distinct Dasatinib-Induced Mechanisms of Apoptotic Response and Exosome Release in Imatinib-Resistant Human Chronic Myeloid Leukemia Cells.

Although dasatinib is effective in most imatinib mesylate (IMT)-resistant chronic myeloid leukemia (CML) patients, the underlying mechanism of its effectiveness in eliminating imatinib-resistant cells is only partially understood. This study investigated the effects of dasatinib on signaling mechanisms driving-resistance in imatinib-resistant CML cell line K562 (K562R(IMT)). Compared with K562 control cells, exsomal release, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling and autophagic activity were increased significantly in K562R(IMT) cells and mTOR-independent beclin-1/Vps34 signaling was shown to be involved in exosomal release in these cells. We found that Notch1 activation-mediated reduction of phosphatase and tensin homolog (PTEN) was responsible for the increased Akt/mTOR activities in K562R(IMT) cells and treatment with Notch1 γ-secretase inhibitor prevented activation of Akt/mTOR. In addition, suppression of mTOR activity by rapamycin decreased the level of activity of p70S6K, induced upregulation of p53 and caspase 3, and led to increase of apoptosis in K562R(IMT) cells. Inhibition of autophagy by spautin-1 or beclin-1 knockdown decreased exosomal release, but did not affect apoptosis in K562R(IMT) cells. In summary, in K562R(IMT) cells dasatinib promoted apoptosis through downregulation of Akt/mTOR activities, while preventing exosomal release and inhibiting autophagy by downregulating expression of beclin-1 and Vps34. Our findings reveal distinct dasatinib-induced mechanisms of apoptotic response and exosomal release in imatinib-resistant CML cells.

Association between miR-212-3p and SOX11, and the effects of miR-212-3p on cell proliferation and migration in mantle cell lymphoma.

To the best of our knowledge, the effect of miR-212-3p on sex-determining region Y-box 11 (SOX11) expression has not been previously investigated and how this effect affects cell proliferation and migration in lymphoma remains unclear. The present study aimed to assess the association between microRNA-212-3p (miR-212-3p) and SOX11, and the effects of miR-212-3p on cell proliferation and migration in mantle cell lymphoma. Cancer tissue and corresponding paracancerous tissue samples were collected from 65 patients with mantle cell lymphoma. The mRNA expression levels of miR-212-3p and SOX11 were analyzed using quantitative PCR, and SOX11 protein expression was determined using western blotting. Following transfection, the miR-212-3p mimic group exhibited a significantly lower SOX11 mRNA and protein expression than the miR-NC group. After 48-72 h of transfection, cell proliferation in the miR-212-3p mimic group was significantly lower than that in the miR-NC group. Furthermore, the miR-212-3p mimic group exhibited significantly lower cell invasion and significantly higher apoptosis than the miR-NC group. The current results suggested that miR-212-3p inhibited lymphoma cell proliferation and migration, and promoted their apoptosis by specifically regulating SOX11. Therefore, miR-212-3p may serve as a novel therapeutic target and marker for lymphoma.

lncRNA SNHG14 promotes oncogenesis and immune evasion in diffuse large-B-cell lymphoma by sequestering miR-152-3p.

This study aimed to explore the role of small nucleolar RNA host gene 14 (SNHG14) in the pathogenesis of diffuse large-B-cell lymphoma (DLBCL). DLBCL cell lines (OCI-Ly7 and OCI-Ly3) and specimens from patients were collected to evaluate the roles of SNHG14 in DLBCL pathogenesis. The results showed that SNHG14 expression increased and miR-152-3p expression decreased in DLBCL tissues and cell lines, indicating a negative correlation between miR-152-3p and SNHG14 expression. Moreover, SNHG14 was found to promote DLBCL growth, migration, and EMT-like processes in vitro, and directly inhibits miR-152-3p gene expression via sequestration of the miR-152-3p transcripts in DLBCL. Additionally, SNHG14/miR-152-3p inhibits apoptosis and promotes cell proliferation on cytotoxic T lymphocytes (CTLs) in DLBCL via the PD-1/PD-L1 checkpoint. Furthermore, both the immune escape and progression of DLBCL are advanced by SNHG14 expression via its interactions with miR-152-3p. Collective, this suggests that SNHG14 is a potential diagnostic, prognostic, and therapeutic target for DLBCL.

Home quarantine compliance is low in children with fever during COVID-19 epidemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak began in China at the end of 2019. The disease is highly infectious. In order to prevent and control the epidemic situation, the state has issued a series of measures to guide the prevention and control of the epidemic. At the same time, it also introduced the measure of home isolation for children with fever. However, due to the nature of children, the implementation of the home isolation turned out to be quite difficult, and questions regarding the home isolation were brought out by parents when seeing doctors. For this reason, we decided to conduct this study. AIM: To study factors that influence home quarantine compliance in children with fever during the COVID-19 epidemic. METHODS: A total of 495 paediatric patients with respiratory tract infection and fever were selected from the general fever clinic at Xiamen Children's Hospital from February 6-27, 2020. On day 8 after the hospital visit, follow-up was conducted by telephone to evaluate the compliance of home quarantine. RESULTS: Among the ten quarantine measures, the proportion of families adhering to keeping 1.5 m distance, proper hand hygiene, wearing masks at home, and proper cough etiquette was very low (< 30% for each measure). Our analysis showed that compliance was related to gender and age of children, gender and age of primary caregiver, number of children in the family, and intensity of information on quarantine measures. We observed that compliance increased with the age of children. Compared with children whose caregivers were young adults, children with elderly caregivers were 2.461 times more likely to show poor compliance. Furthermore, children who received intensive information on quarantine measures had significantly better compliance. CONCLUSION: Compliance of children with fever to quarantine measures at home is low during the COVID-19 epidemic. Strengthening education on the quarantine measures is critical to improve compliance, in particular in young children with elderly caregivers.

[Role of probiotics in the prevention of neonatal necrotizing enterocolitis: A case-control study].

OBJECTIVE: To assess the role of probiotics in the prevention of neonatal necrotizing enterocolitis (NEC) and to investigate the risk factors for NEC. METHODS: A total of 2528 hospitalized neonates between January 2002 and May 2005 were assigned into either receiving prophylactic use of probiotics bifoco (Prevention group, n=1182) or without probiotics supplementation (Control group, n = 1346). The incidence of NEC was compared between the two groups. The risk factors for NEC were investigated by conditional logistic regression multifactorial analysis. RESULTS: There were 19 cases of NEC in the Control group (1.41%), but only 6 cases in the Prevention group (0.51%) (P < 0.05). Gestational age (OR = 5.521), hypoxicdouble ended arrowischemic encephalopathy (OR = 3.887), specticemia (OR = 4.854) and critical illness scores (OR = 5.989) were the risk factors for NEC, while the prophylactic use of probiotics was an independent protective factor for NEC (OR = 0.255). CONCLUSIONS: The prophylactic use of probiotics may reduce the incidence of NEC in neonates.