Combination therapy is used to optimize anticancer efficacy and reduce the toxicity and side-effects of drugs upon systemic administration. Ultrasound (US) combined with micro-bubbles (UM) enhances the intracellular uptake of cytotoxic drugs by tumor cells, particularly drug-resistant cells. In the present study, low-frequency and low-energy US (US irradiation conditions: frequency, 21 kHz; power density, 0.113 W/cm2; exposure time, 2 min at a duty cycle of 70%; and valid treatment time, 84 sec) were used in combination with microbubbles (100 μl/ml) to deliver mitoxantrone HCl (MIT) to DU145 cells. The results showed that UM did not change the cell viability in the short- or long-term. However, UM statistically enhanced the therapeutic effects and up to 31.26±3.34% of the cells exposed to UM were permeabilized compared with 9.74±2.55% of cells in the control, when using calcein (MW, 622.53) as a fluorogenic marker. Notably, UM affected the migration capability of the DU145 cells at 6 h post-treatment. In conclusion, the ultrasonic parameters used in the present study enhanced the chemotherapeutic effect and reduced the unwanted side-effects of MIT.

Marsupialisation or decompression is frequently performed as a conservative therapy for keratocystic odontogenic tumours (KCOTs). Positive podoplanin (PDPN) expression in the epithelium of KCOT has been previously reported and may be associated with neoplastic invasion. In the present study, changes in PDPN expression were observed in the epithelium of KCOTs following decompression. In total, 16 pairs of paraffin-embedded tissue specimens obtained at the time of decompression and at two-stage curettage or enucleation were collected and immunohistochemically examined using an antibody against PDPN. The intensity of PDPN staining was evaluated with a semi-quantitative detection method and statistically analysed. The immunohistochemical reactivity of PDPN was consistently markedly positive in 93.8% of KCOT samples prior to decompression. The positive staining was immunolocalised to the cell membrane and cytoplasm of cells in the basal layer and extended into the suprabasal layer for two to three cell layers. At the time of curettage, 2 of the 16 (12.5%) cases were completely negative, 11 of the 16 (68.8%) cases were locally positive and 3 of the 16 (18.7%) cases showed a 'linear staining' pattern, as the PDPN-positive cells were restricted to within the single basal layer. The expression level of PDPN was significantly decreased (P<0.05) and a significant loss or reduction of PDPN expression was observed in KCOTs following decompression. Larger sample groups are required to further verify this result.

Methylation of histone H4 lysine 20 (H4K20) has been associated with cancer. However, the functions of the histone methyltransferases that trigger histone H4K20 methylation in cancers, including suppressor of variegation 4-20 homolog 1 (Suv4-20h1), remain elusive. In the present study, it was demonstrated that the knockdown of the histone H4K20 methyltransferase Suv4-20h1 resulted in growth inhibition in chronic myeloid leukemia K562 cells. Disruption of Suv4-20h1 expression induced G1 arrest in the cell cycle and increased expression levels of cyclin dependent kinase inhibitor 1A (p21WAF1/CIP1), an essential cell cycle protein involved in checkpoint regulation. Chromatin immunoprecipitation analysis demonstrated that Suv4-20h1 directly binds to the promoter of the p21 gene and that methylation of histone H4K20 correlates with repression of p21 expression. Thus, these data suggest that Suv4-20h1 is important for the regulation of the cell cycle in K562 cells and may be a potential therapeutic target for leukemia.

Cell division cycle-associated 2 (CDCA2) plays an important role in regulating chromosome structure during mitosis. It is highly expressed in oral squamous cell carcinoma, neuroblastoma and lung adenocarcinoma, and its upregulation is positively associated with tumor progression. However, the expression, biological function and underlying mechanisms of the role of CDCA2 in clear cell renal cell carcinoma (ccRCC) remain poorly understood. In the present study, CDCA2 was demonstrated to be upregulated in ccRCC tissues compared with normal kidney tissue, where higher expression was generally associated with the degree of malignancy. Small interfering RNA-mediated knockdown of CDCA2 expression inhibited the viability and proliferation of 786-O and CAKI-1 cells, as measured by an MTT assay, colony formation assay and flow cytometry. Furthermore, western blot analysis suggested that CDCA2 regulates cell proliferation through the cell cycle-associated proteins cyclin D1 and cyclin dependent kinase 4, and the apoptotic protein Bcl-2. In conclusion, the present study indicated that CDCA2 may be an important factor in ccRCC progression and could be a potential therapeutic target in this disease.

Hepatocellular carcinoma (HCC) remains a challenge in the medical field due to its high malignancy and mortality rates particularly for HCC, which has developed multidrug resistance. Therefore, the identification of efficient chemotherapeutic drugs for multidrug resistant HCC has become an urgent issue. Natural products have always been of significance in drug discovery. In the present study, a cell-based method was used to screen a natural compound library, which consisted of 78 compounds, and the doxorubicin-resistant cancer cell line, HepG2/ADM, as screening tools. The findings of the present study led to the shortlisting of one of the compounds, digitoxin, which displayed an inhibitory effect on HepG2/ADM cells, with 50% inhibitory concentration values of 132.65±3.83, 52.29±6.26, and 9.13±3.67 nM for 24, 48, and 72 h, respectively. Immunofluorescence, western blotting and cell cycle analyses revealed that digitoxin induced G2/M cell cycle arrest via the serine/threonine-protein kinase ATR (ATR)-serine/threonine-protein kinase Chk2 (CHK2)-M-phase inducer phosphatase 3 (CDC25C) signaling pathway in HepG2/ADM cells, which may have resulted from a DNA double-stranded break. Digitoxin also induced mitochondrial apoptosis, which was characterized by changes in the interaction between Bcl-2 and Bax, the release of cytochrome c, as well as the activation of the caspase-3 and -9. To the best of our knowledge, the present study is the first report that digitoxin displays an anti-HCC effect on HepG2/ADM cells through G2/M cell cycle arrest, which was mediated by the ATR-CHK2-CDC25C signaling pathway and mitochondrial apoptosis. Therefore, digitoxin could be a promising chemotherapeutic agent for the treatment of patients with HCC.

Immunotherapy based on the tumor microenvironment is a feasible method for treating cancer; therefore, it is necessary to investigate the immune microenvironment of pancreatic cancer and the influencing factors of the immune microenvironment. Chemokines are an important factor affecting the tumor immune microenvironment. In the present study, chemokines or chemokine receptors were screened to identify those differentially expressed in pancreatic cancer compared with normal controls and associated with patient prognosis. Chemokines or chemokine receptors that are differentially expressed in pancreatic cancer tumor tissues were initially screened using the Gene Expression Omnibus database. Next, survival analysis was performed using GEPIA, a website based on The Cancer Genome Atlas (TCGA) database. Immunohistochemical staining of CXCL5 was performed in tissue microarrays (TMAs) containing 119 cases of pancreatic cancer. Histochemistry score (H-SCORE) was used to evaluate the expression of CXCL5. Next, association analysis of the H-SCORE of CXCL5 and the clinical characteristics of patients was performed, as well as Kaplan-Meier survival and Cox multivariate regression analyses. The results of the bioinformatics analysis demonstrated that CXCL5 was highly expressed in pancreatic cancer tissues. High expression of CXCL5 in pancreatic cancer tissues was associated with a poor prognosis in patients in TCGA cohort. The expression level of CXCL5 in tumor tissues was significantly higher compared with that in adjacent peritumoral normal tissues in the immunohistochemical analysis. There was no significant association between CXCL5 expression in pancreatic cancer tumor tissues and clinicopathological factors. Patients with pancreatic cancer with high CXCL5 expression had a poor prognosis, as determined by Kaplan-Meier survival analysis based on the TMA dataset. The results of Cox multivariate regression analysis showed that CXCL5 was an independent factor for a poor prognosis in patients with pancreatic cancer. In conclusion, the results of the present study revealed that the chemokine CXCL5 was highly expressed in pancreatic cancer tissues; high CXCL5 expression was associated with a poor prognosis in patients with pancreatic cancer.

Correlation of p16 and cyclin D1 expression with the incidence and prognosis of cardiac carcinoma was investigated. Thirty-six patients with cardiac carcinoma treated in The Second Affiliated Hospital of Zhengzhou University were selected. After the radical operation of cardiac carcinoma, carcinoma tissues were taken, and the corresponding para-carcinoma tissues were used as controls. p16 and cyclin D1 messenger ribonucleic acid (mRNA) and protein expression in cardiac carcinoma tissues and para-carcinoma tissues were detected via quantitative polymerase chain reaction (qPCR) and western blot analysis. The survival time and pathological conditions of patients with cardiac carcinoma were recorded in detail, and correlation of p16 and cyclin D1 with incidence and prognosis of cardiac carcinoma was studied. In cardiac carcinoma tissues, the p16 mRNA and protein expression levels were significantly lower than those in para-carcinoma tissues (P<0.01), but the cyclin D1 mRNA and protein expression levels were significantly higher than those in para-carcinoma tissues (P<0.01). The expression of p16 and cyclin D1 protein had correlation with the tumor size, lymph node metastasis and tumor-node-metastasis stage of cardiac carcinoma (P<0.01). There was a negative correlation between expression of p16 and cyclin D1 in cardiac carcinoma (P<0.01). According to Kaplan-Meier survival analysis, the survival rate of patients with high expression of p16 was obviously higher than that of patients with low expression of p16 (P<0.01), while the survival rate of patients with high expression of cyclin D1 was obviously lower than that of patients with low expression of cyclin D1 (P<0.01). Both p16 and cyclin D1 are closely related to the incidence and prognosis of cardiac carcinoma, which may become indexes for the incidence and prognosis of cardiac carcinoma.

Melanocyte proliferating gene 1 (MYG1) is an exonuclease that participates in RNA processing and is required for normal mitochondrial function. However, its role in tumorigenesis remains unknown. The present study aimed to investigate the role of MYG1 and its underlying mechanisms in human lung adenocarcinoma (LUAD). The expression levels of MYG1 in tumor tissues of patients with LUAD were obtained from public cancer databases and analyzed using the UALCAN online software. The association between MYG1 expression levels and the prognosis of patients with LUAD was analyzed using the Kaplan-Meier plotter. In addition, the role of MYG1 in the LUAD A549 and H1993 cell lines was determined by knocking down MYG1 expression with a specific small interfering RNA or by overexpressing it with a MYG1-containing plasmid. The results demonstrated that MYG1 expression levels were upregulated in LUAD tissues compared with those in normal lung tissues from healthy subjects, and high MYG1 expression levels were associated with an unfavorable prognosis. MYG1 promoted the proliferation, migration and invasion of A549 and H1993 cells. In addition, MYG1 inhibited autophagy via the AMP-activated protein kinase/mTOR complex 1 signaling pathway. Collectively, the present results suggested that MYG1 may serve an oncogenic role in LUAD and may be a potential therapeutic target for LUAD.

Level of mRNA expression and gene polymorphism of human 8-hydroxyguanine glycosidase 1 (hOGG1) in patients with non-small cell lung cancer (NSCLC) were investigated. A polymorphism analysis of hOGG1 gene rs1052133 locus in 182 NSCLC patients (NSCLC group) surgically treated in Xiang Yang No. 1 People's Hospital, Hubei University of Medicine from January 2008 to January 2012 and 200 healthy individuals (control group) was performed. The expression level of hOGG1 was compared between cancer tissues and adjacent tissues of NSCLC patients, and the survival rate was analyzed. The expression level of hOGG1 was significantly higher in cancer tissues than that in adjacent tissues (P<0.001). Taqman probe method was used to detect the genotypes of hOGG1 polymorphism locus rs1052133, with the genotype distribution frequencies of NSCLC group (P=0.411) and control group (P=0.354) consistent with the Hardy-Weinberg equilibrium. The proportion of C/C gene was significantly higher in NSCLC group than that in control group (P=0.008, OR=2.2, 95%, CI=1.27-4.52). The median value of the hOGG1 expression level in detection results as the boundary, NSCLC patients were divided into hOGG1 high expression group (≥3.61) with 91 cases and hOGG1 low expression group (<3.61) with 91 cases. The 1-, 2- and 3-year survival rates of patients in hOGG1 low expression group were significantly higher than those in hOGG1 high expression group (P=0.007). The 3-year survival rate in hOGG1 low expression group is significantly higher than that in hOGG1 high expression group (P=0.007). The sensitivity, specificity and AUC of hOGG1 to patient survival prediction were 83.33%, 64.29%, and 0.816, respectively. In conclusion, hOGG1 is highly expressed in NSCLC tissues. Compared to S/S and S/C genotypes, the C/C gene was found to be more common in NSCLC group than in control group. Thus, hOGG1 has a high predictive value for patient survival.

Endometrial cancer (EC) is a multi-factorial disease of which pathogenesis has not been fully elucidated. The function and underlying mechanism of microRNA-20a-5p (miR-20a-5p) in EC remain poorly understood. The present study aimed to analyze the association between miR-20a-5p expression and the clinicopathological characteristics of patients with EC. Whether miR-20a-5p could inhibit EC progression by targeting janus kinase 1 (Jak1) was subsequently investigated. To do so, human EC tissues and paracancerous tissues were collected from 47 patients with EC. miR-20a-5p and Jak1 mRNA and protein expression was determined by reverse transcription quantitative PCR and western blotting, respectively. Cell proliferation, invasive ability and adhesion were investigated by MTT, Matrigel invasion and cell adhesion assays, respectively. Dual luciferase reporter assay was used to verify whether miR-20a-5p could directly target Jak1. The results demonstrated that miR-20a-5p was downregulated and that Jak1 was upregulated in EC tissues compared with paracancerous tissues. In addition, miR-20a-5p expression and Jak1 expression level were negatively correlated in EC tissues. miR-20a-5p expression was also significantly associated with the depth of myometrial invasion, FIGO stage, histologic grade and lymph node metastasis in patients with EC. Furthermore, Jak1 was identified as a new direct target of miR-20a-5p, and Jak1 overexpression was demonstrated to reverse the effects of miR-20a-5p-mimic on EC cell proliferation, invasive ability and adhesion. Taken together, the results from this study revealed for the first time that miR-20a-5p expression was significantly associated with the clinicopathological characteristics of patients with EC. These findings suggested that miR-20a-5p may act as a tumor suppressor in EC, in part through decreasing Jak1 expression. miR-20a-5p and Jak1 may therefore serve as potential therapeutic targets in EC.

Exosome complex (EXOSC) genes, which encode a multi-protein intracellular complex, mediate the degradation of various types of RNA molecules. EXOSCs, also known as polymyositis/scleroderma complexes, exist in eukaryotic cells and archaea, and primarily mediate 3' to 5'mRNA degradation. However, how EXOSC genes are implicated in processes of B-cell immune-associated pathways and B-cell tumorigenesis remains unclear. The present bioinformatics study indicated that 6 of 10 EXOSC genes, particularly the EXO.index, were able to predict the survival of patients with mantle cell lymphoma (MCL), by analyzing gene expression profiles of 123 patients with MCL from the Gene Expression Omnibus database. The results suggested that EXOSC gene expression may be a molecular marker for MCL. Compared with the whole transcript profile, patients with MCL with a high EXO.index exhibited poorer survival and decreased RNA levels, which was also verified in a second dataset. The EXOSC genes may be associated with DNA repair and B-cell activation pathways, which may be the cause of poorer survival of patients with MCL.

Advanced prostate cancer is difficult to treat due to androgen resistance, its deep location and blood tumor barriers. Low-frequency ultrasound (LFU) has potential clinical applications in the treatment of prostate cancer due to its strong penetrability and high sensitivity towards tumor cells. Simvastatin has often been administered as a preventive agent in prostate tumors. The aim of the present study was to investigate the enhanced effects of LFU and microbubbles in combination with simvastatin, in inhibiting cell viability and promoting apoptosis of androgen-independent prostatic DU145 cells. Cultured DU145 cells were divided into six groups based on the combination of treatments as follows: Control, LFU, LFU and microbubbles (LFUM), simvastatin, LFU and simvastatin, LFUM and simvastatin. The cells were treated by LFU (80 kHz) continuously for 30 sec with an ultrasound intensity of 0.45 W/cm2 and a microbubble density of 20%. Simvastatin was added 30 h prior to the ultrasound exposure. The results indicated that cell viability was marginally reduced in the LFU and simvastatin alone treatment groups compared with the control 24 h following ultrasound exposure. The combination of LFU, with microbubbles or simvastatin, potentiated the growth inhibition; the greatest inhibition was observed in the cells that were subject to treatment with LFUM and simvastatin in combination. Furthermore, this inhibitory effect was enhanced in a time-dependent manner. For cell apoptosis, a low dose of simvastatin had no apparent affect on the DU145 cells, while LFU marginally promoted cell apoptosis. Microbubbles or simvastatin increased the apoptosis rate of the DU145 cells, however, the combination of LFUM and simvastatin induced a strong synergistic effect on cell apoptosis. Western blotting analysis demonstrated a high expression level of caveolin-1 in resting DU145 cells. LFUM or combined LFU and simvastatin resulted in a greater reduction in the expression compared with the control group (P<0.05). The expression of caveolin-1 was lowest in the LFUM combined with simvastatin treatment group. The expression of phospho-Akt (p-Akt) was consistent with caveolin-1, with the lowest expression levels of p-Akt observed in the cells that were treated with the combination of LFUM and simvastatin. The results indicate that LFUM in combination with simvastatin may additively or synergistically inhibit cell viability and induce apoptosis of DU145 cells by downregulating caveolin-1 and p-Akt protein expression.

Kin17 protein is ubiquitously expressed in mammals and is correlated with vital biological functions. However, little is known about the role of Kin17 in the proliferation of hepatocellular carcinoma cells. The aim of the present study was to investigate whether the upregulation of Kin17 can promote the growth of hepatocellular carcinoma cells. A series of assays was performed to study the effect of Kin17 in the proliferation of hepatocellular carcinoma cells in vitro and in vivo. The western blotting results revealed that Kin17 expression was increased in hepatocellular carcinoma tissues compared with that of the corresponding normal tissues. Moreover, ectopic upregulation of Kin17 expression promoted the growth of hepatocellular carcinoma cells in vitro and in vivo. These results indicated that Kin17 is involved in the tumorigenesis of hepatocellular carcinoma, and that Kin17 has the potential to serve as a therapeutic target for hepatocellular carcinoma.

Heterogeneous ribonuclear protein C2 (hnRNPC2), an RNA binding protein, is a component of hnRNPC which is upregulated in many tumors. Multinucleation exists in many tumors and is positively correlated with tumor grade. To uncover the correlation between hnRNPC2 and multi-nucleation in hepatocellular carcinoma SMMC-7721 cells, we constructed a pEGFP-hnRNPC2 vector and transfected it into cancer cells. Our results revealed that overexpression of hnRNPC2 induced multinucleation in SMMC-7721 cells. Tracking tests indicated that the induced multinucleated cells were unable to recover to mononuclear cells and finally died as a result of defects in cell division. Furthermore, Aurora B, which was localized at the midbody and plays a role in cytokinesis, was repressed in hnRNPC2-overexpressing cells, whose knockdown by RNA interference also induced multinucleation in SMMC-7721 cells. Quantitative polymerase chain reaction (qPCR) and mRNA-protein co-immunoprecipitation results revealed that Aurora B mRNA did not decrease in hnRNPC2-overexpressing cells, instead it bound more hnRNPC2 and less eIF4E, an mRNA cap binding protein and translational initiation factor. Moreover, hnRNPC2 bound more eIF4E in hnRNPC2-overexpressing cells. These results indicate that hnRNPC2 repressed Aurora B binding with eIF4F, which must bind with Aurora B mRNA in order to initiate its translation. This induced multinucleation in hepatocellular carcinoma cells. In addition, hnRNPC2 accelerated hepatocellular carcinoma cell proliferation. Collectively, these data suggest that hnRNPC2 may be a potential target for hepatocellular carcinoma cell diagnosis and treatment.

Hodgkin's lymphoma (HL) is a common hematologic tumor, and the incidence is increasing. At present, it is considered that miRNAs are closely related to HL. Substantial attention has been paid to the effects of miRNA on the pathophysiological process of HL. This study was focused on the potential role of miR-24-3p in HL by targeting DEDD. The reverse transcription-quantitative PCR (RT-qPCR) results demonstrated that miR-24-3p expression was highly elevated and DEDD expression reduced inversely in HL tissues compared to adjacent tissues. According to the results of CKK-8 assays, miR-24-3p was able to accelerate HL cell proliferation. In addition, the results of the Transwell assays also indicated that miR-24-3p promoted the invasion and migration abilities of HL cells. Moreover, the results demonstrated that miR-24-3p inhibited DEDD expression. Hence, the present study revealed that miR-24-3p could accelerate HL development through inhibiting DEDD.

Microtubule associated serine/threonine kinase-like (MASTL) is the functional mammalian ortholog of Greatwall kinase (Gwl), which was originally discovered in Drosophila. Gwl is an essential kinase for accurate chromosome condensation and mitotic progression, and inhibits protein phosphatase 2A (PP2A), which subsequently dephosphorylates the substrates of cyclin B1-cyclin-dependent kinase 1, leading to mitotic exit. Previous studies have indicated that MASTL has a critical function in the regulation of mitosis in HeLa and U2OS cell lines, though there is currently limited evidence for the involvement of MASTL in hepatocarcinogenesis. The results of the present study revealed that MASTL was inducible by the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), which promoted the proliferation and mitotic entry of human liver cancer cells. It was also determined that MASTL was significantly overexpressed in cancerous liver tissues compared with non-tumor liver tissues. Mechanistically, stimulation by IL-6 and TNF-α induced the trimethylation of histone H3 lysine 4 (H3K4Me3) at the MASTL promoter to facilitate chromatin accessibility. Additionally, H3K4Me3 was associated with the activation of nuclear factor-κB, which subsequently upregulated MASTL expression. These findings suggested that MASTL may have pivotal functions in the development of hepatocarcinoma, and that it may be a potential target for treatment.

Monocytic leukemia-associated antigen-34 (MLAA-34) is a novel monocytic leukemia-associated antigen and a candidate oncogene. The aim of the present study was to investigate the involvement of the MLAA-34 gene in acute myeloid leukemia (AML). MLAA-34 expression level, chromosome location, gene copy number and single nucleotide polymorphisms (SNPs) of 40 patients with AML and 5 healthy volunteers were analyzed by reverse transcription-polymerase chain reaction, fluorescence in situ hybridization and DNA sequencing. The effects of MLAA-34 mutation on overall survival (OS) and progression-free survival (PFS) of patients with AML were also analyzed. MLAA-34 was significantly upregulated in patients with AML when compared with volunteer controls, and this upregulation was associated with a C59T SNP site located in the second exon of MLAA-34. MLAA-34 was mapped to 13q14.2 and no translocation was observed in patients with AML. In addition, this SNP site is affinitive to the well-known molecular markers of AML, including Fms-like tyrosine kinase 3 and DNA methyltransferase 3A, as well as extramedullary lesions, periphery leukocyte numbers, remission and cytogenetic abnormalities of patients with AML. Patients with AML with MLAA-34 C59T mutations had significantly shorter OS and PFS times compared with that of patients without C59T mutations. The present findings indicated that the MLAA-34 C59T mutation was a high-risk factor for recurrence of AML, and may be a candidate target for AML therapy.

The majority of cancer stem cells exist in the G0, or quiescent phase of the cell cycle. However, the cells can escape quiescence following routine radiotherapy and chemotherapy, resulting in tumor recurrence. Presently, achieving the accurate regulation of cancer stem cell growth in order to study a specific state, including the quiescent (mostly G0 or G1 phase), proliferative (mostly S phase) or differential (mostly G2/M phase) states, can be challenging. This makes the determination of cell cycle state-specific characteristics and analysis of potential intervention treatments difficult, particularly for quiescent cells. Breast cancer stem cells were cultured on a soft or hard agar matrix surface in the presence or absence of stem cell growth factors. Cells could be successfully limited in either the quiescent, proliferative or differentiated states. These findings provide a foundation for further study of the cell cycle in breast cancer stem cells.

Expression level of miR-98 in diabetic colon cancer (CRC) tissues and the regulation mechanism of colon cancer cell proliferation and invasion ability were studied. Forty patients with type 2 diabetes mellitus complicated with colon cancer, 40 colon cancer patients, and 40 patients with diabetic colonoscopy were enrolled between January 2017 and January 2018. Real-time quantitative PCR was used to detect the expression level of miR-98. After SW480 cells were transfected with miR-98 mimics or control simulants, the proliferation of cancer cells was detected by MTT assay, and the invasion ability of cancer cells was detected by Transwell cell invasion assay. The dual luciferase assay was used to detect the binding relationship between miR-98 and IGF1R. Western blot analysis was used to detect the expression of IGF1R protein in tumor tissues of patients with diabetes mellitus and colon cancer. Compared with diabetic patients, the expression level of miR-98 was decreased in colon cancer patients. Compared with tumor tissues of colon cancer patients, the expression level of miR-98 was significantly decreased in diabetic colon cancer tissues. Compared with the commonly cultured colon cancer SW480 cells, the expression level of miR-98 was significantly decreased in SW480 cells cultured under high glucose conditions. Increased expression of miR-98 inhibits colon cancer cell proliferation and invasion. miR-98 can target and bind to IGF1R and inhibit its expression level. IGF1R is upregulated in diabetic colon cancer tissue. miR-98 inhibits proliferation and invasion of diabetic colon cancer by targeting IGF1R. The expression level of miR-98 in diabetic colon cancer tissues is lower than that in colon cancer tissues. miR-98 can inhibit the proliferation and invasion of colon cancer cells by targeting the target gene IGF1R. miR-98 may be a potential biological target for the treatment of patients with diabetes and colon cancer.

Vincristine is one of the most common anticancer drugs clinically employed in the treatment of various malignancies. A major side effect associated with vincristine is the development of neuropathic pain, which is not readily relieved by available analgesics. Although efforts have been made to identify the pathogenesis of vincristine-induced neuropathic pain, the mechanisms underlying its pathogenesis have not been fully elucidated. In the present study, a neuropathic pain model was established in Sprague-Dawley rats by intraperitoneal injection of vincristine sulfate. The results demonstrated that vincristine administration induced the upregulation of transient receptor potential cation channel subfamily V member 1 (TRPV1) protein expression and current density in dorsal root ganglion (DRG) nociceptive neurons. Consistently, inhibition of TRPV1 with capsazepine alleviated vincristine-induced mechanical allodynia and thermal hyperalgesia in rats. Furthermore, vincristine administration induced the upregulation of tumor necrosis factor (TNF)-α production in DRGs, and inhibition of TNF-α synthesis with thalidomide in vivo reversed TRPV1 protein expression, as well as pain hypersensitivity induced by vincristine in rats. The present results suggested that TNF-α could sensitize TRPV1 by promoting its expression, thus leading to mechanical allodynia and thermal hyperalgesia in vincristine-treated rats. Taken together, these findings may enhance our understanding of the pathophysiological mechanisms underlying vincristine-induced pain.