Circular RNA circ-RNF121 contributes to cisplatin (DDP) resistance of non-small-cell lung cancer cells by regulating the miR-646/SOX4 axis.

Chemo-resistance is considered a major obstacle in the clinical treatment of non-small-cell lung cancer (NSCLC). Circular RNA (circRNA) circ-RNF121 (hsa_circ_0023404) has been identified to be related to the cisplatin (DDP) resistance. However, the role and mechanism of circ-RNF121 in the DDP resistance in NSCLC are still unknown. Real-time quantitative PCR (RT-qPCR) was applied to detect the levels of circ-RNF121, microRNA-646 (miR-646) and SRY-related HMG box transcription factor 4 (SOX4). Cell viability, proliferation, apoptosis, migration, invasion and cell cycle progression were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, flow cytometry, wound-healing, transwell and flow cytometry assays, severally. The binding relationship between miR-646 and circ-RNF121 or SOX4 was predicted by the circular RNA interactome or Target Scan Human7.2 and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. SOX4 protein level was measured by western blot assay. The biological role of circ-RNF121 on NSCLC tumor growth and drug resistance was examined by the xenograft tumor model in vivo. Circ-RNF121 and SOX4 were increased, and miR-646 was declined in DDP-resistant NSCLC tissues and cells. Furthermore, the circ-RNF121 deficiency could enhance DDP sensitivity by inhibiting cell proliferation, migration, invasion, cell cycle progression and promoting apoptosis in DDP-resistant NSCLC cells in vitro. Mechanically, circ-RNF121 served as a sponge of miR-646 to increase SOX4 expression. Circ-RNF121 knockdown improved the drug sensitivity of NSCLC in vivo. Circ-RNF121 silencing could reduce the DDP resistance of NSCLC cells by regulating SOX4 expression via miR-646. These findings hinted at a promising therapeutic target for NSCLC treatment.

LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression.

BACKGROUND: Lung adenocarcinoma (LAD) is a prevalent type of bronchogenic malignant tumor and one of the most critical factors related to human death. Long noncoding RNAs (lncRNAs) are involved in many complex biological processes and have been emerged as extremely important regulators of various cancers. LINC02418, a novel lncRNA, hasn't been mentioned in previous studies on cancer development. Therefore, it's important to define the potential function of LINC02418 in LAD. METHODS: Gene expression was examined by RT-qPCR or western blot. CCK-8, colony formation, TUNEL, and transwell assays were utilized to study the role of LINC02418 in LAD. The interaction of miR-4677-3p with LINC02418 (or KNL1) was verified through luciferase reporter, RIP and RNA pull-down assays. RESULTS: High expression of LINC02418 was observed in LAD specimens and cells. Downregulation of LINC02418 obstructed the proliferation and motility of LAD cells. Moreover, LINC02418 negatively modulated miR-4677-3p expression and miR-4677-3p overexpression could repress cell proliferation and migration. Moreover, kinetochore scaffold 1 (KNL1) expression was negatively modulated by miR-4677-3p but positively regulated by LINC02418. Furthermore, miR-4677-3p could bind with LINC02418 (or KNL1). Finally, KNL1 overexpression reversed the inhibitory function of LINC02418 deficiency in the malignant behaviors of LAD cells. CONCLUSIONS: LINC02418 contributes to the malignancy in LAD via miR-4677-3p/KNL1 signaling, providing a probable therapeutic direction for LAD.

Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway.

Hepatocellular carcinoma (HCC) is a devastating and highly metastatic cancer worldwide. Metformin (MET) is the priority drug for treatment of type 2 diabetes; however, it possesses multiple biological effects like anticancer and hepatoprotective activity. Herein, we examined the effects of aloin (barbaloin) and MET as well as combination treatment in HCC cell line in vitro and in vivo. As a result, aloin and MET alone exhibited inhibitory effects on proliferation and invasion of HepG2 and Bel-7402 cells. Specially, combination treatment of aloin and MET showed enhanced inhibitory effects in vitro. Aloin and MET alone induced apoptosis and autophagy in vitro. Similarly, aloin and MET cooperated to promote apoptosis and autophagy in HepG2 and Bel-7402 cells. In the HepG2 xenograft models, aloin in combination with MET confine tumor growth and facilitate apoptosis and autophagy. Both the in vitro and in vivo results showed that aloin and MET alone as well as combination treatment activated the PI3K/AKT/mTOR pathway. Overall, our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway.

WITHDRAWN: The anti-growth and anti-metastasis effects of Schisandrin B on hepatocarcinoma cells in vitro and in vivo.

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Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

OBJECTIVES: Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. METHODS: PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. RESULTS: Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). CONCLUSIONS: Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

The efficacy and safety of sirolimus-based graft-versus-host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy and safety of sirolimus (SIR)-based graft-versus-host disease (GVHD) prophylaxis in patients who were subjected to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain to be clarified; this meta-analysis was conducted to evaluate these factors. STUDY DESIGN AND METHODS: Data from original research were obtained from PubMed, Embase, and Cochrane central register of controlled trials databases. Randomized controlled trials (RCTs) evaluating the efficacy of SIR-based prophylaxis in allo-HSCT were included. The risk ratio (RR), with a 95% confidence interval (CI), was used to pool data. The random effects model was used, irrespective of the presence or absence of heterogeneity. RESULTS: Five RCTs were included in the meta-analysis. SIR was observed to significantly decrease the incidence of Grade II to IV acute GVHD (aGVHD; RR, 0.65; 95% CI, 0.47-0.89). However, the incidence of Grade III to IV aGVHD and chronic GVHD was not decreased (RR, 0.91; 95% CI, 0.59-1.40; RR, 1.04; 95% CI, 0.88-1.23, respectively). An analysis of the toxic effects of SIR revealed that SIR effected a significant increase in the incidence of sinusoidal obstructive syndrome (RR, 2.24; 95% CI, 1.26-4.01), while that of thrombotic microangiopathy was not significantly increased (RR, 2.48; 95% CI, 0.87-7.06). Moreover, SIR did not improve event-free survival and overall survival (RR, 0.97; 95% CI, 0.85-1.10; and RR, 0.92; 95% CI, 0.82-1.02, respectively). CONCLUSION: This meta-analysis indicated that the SIR-based regimen is an effective and safe alternative prophylaxis strategy for GVHD.

[Radioprotective effect of rmIL-12 on mice irradiated by γ-ray].

The aim of this study was to investigate the radioprotective effect of recombinant murine interleukin 12 (rmIL-12) on mice irradiated by γ-ray. Fifty- six BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group,rmIL-12 treated group and recombinant murine thrombopoietin (rmTPO) treated group.The 5 and 20 µg/kg of rmIL-12 were administrated intraperitoneally at 24 h before irradiation respectively (low and high dose rmIL-12 treated group), 15 µg/kg of rmTPO was administrated subcutaneously at 30 min and 24 h following irradiation in rmTPO treated group. The general conditions of mice were observed twice a day, the changes in body weight and peripheral blood cell counts were examined once every three days, bone marrow cells were collected to perform colony cultivation at day 14 and 28 after irradiation. The results showed that the general conditions of mice in rmIL-12 treated group were better than those in irradiation control group. Compared with the irradiation control group,5 and 20 µg/kg rmIL-12 treatment significantly promoted platelet recovery, resulting in less profound nadirs (15.9% vs 8.1%,18.2% vs 8.1%,P < 0.01) and rapid recovery to normal levels (11 days vs 14 days). WBC count recovery rate in rmIL-12 treated group was faster than that in the irradiation control group. The WBC and platelet count recovery rate in 5 µg/kg rmIL-12 treated group were as fast as that in the rmTPO treated group, both of which were slower than that in 20 µg/kg rmIL-12 treated group (P > 0.05). Semi-solid bone marrow cell culture also demonstrated that rmIL-12 could stimulate bone marrow cells to form more CFU-Mix than those in the irradiation control group in vitro at day 14 and 28 after irradiation(P < 0.01).There was no significant difference between rmIL-12 and rmTPO treated groups (P > 0.05), CFU-GM counts in 5 µg/kg rmIL-12 treated group and rmTPO treated group at day 28 after irradiation were higher than those in irradiation control group(P < 0.05), but less than those in 20 µg/kg rmIL-12 treated group (P < 0.05). It is concluded that rmIL-12 has a significant radioprotective effect on mice irradiated by γ-ray.

[Therapeutic effect of rmIL-12 combined with G-CSF on acute radiation sickness produced by γ-ray irradiation in mice].

The aim of this study is to observe the therapeutic effect of recombinant murine interleukin 12 (rmIL-12) combining with granulocyte colony stimulating factor (G-CSF) on mice irradiated by γ-rays. 56 BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group, rmIL-12 treatment group, G-CSF treatment group and combination therapy (rmIL-12 plus G-CSF) group. rmIL-12 20 µg/kg was administrated intraperitoneally at 1 h following irradiation, and was administrated every 3 days after irradiation for 4 times in rmIL-12 treatment group. G-CSF 100 µg/kg was administrated subcutaneously the 2 h following irradiation for 14 d in G-CSF treatment group. The dose and method of rmIL-12 and G-CSF in combination therapy group were same as in rmIL-12 group and G-CSF group. The general status of mice were observed twice a day, the changes in body weight, peripheral blood cell (WBC and Plt) counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on day 14 and 28 after irradiation. The results showed that WBC count recovery time in combination therapy group was significantly earlier than that of the control group (7 d vs 11 d), WBC count recovery velocity in the combination therapy group was no significant different from that of the G-CSF treatment group. Combined therapy significantly promoted Plt count recovery, resulting in less profound nadirs (16.5% vs 8.1%, P < 0.01) and rapid recovery to normal levels (11 d vs 14 d), Plt count recovery velocity in the combination therapy group was no significant different from that of the rmIL-12 treatment group. Culture of bone marrow cells in semi-solid medium also demonstrated that combination of rmIL-12 and G-CSF could stimulate bone marrow cells to form more CFU-GM and CFU-Mix than those of the irradiation control group in vitro on day 14 and 28 after irradiation (P < 0.05). It is concluded that the combination of rmIL-12 and G-CSF can significantly accelerate the recovery of hematopoietic function in mice with acute radiation sickness.