AIM:To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.
METHODS:
Lymph node (LN) metastasis is often an early event in the progression of malignant tumors and it contributes to the majority of cancer mortalities. MiRNAs play key roles in tumor metastasis. This study aimed to investigate the specific miRNAs as putative indicators of metastasis early diagnosis for non-small cell lung cancer (NSCLC). In this study, five NSCLC cases with LN metastasis and four cases without metastasis (NLN) were enrolled for Agilent Human miRNA array. The interested differentially expressed miRNA was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the LN metastasis (n = 46) and NLN (n = 39) groups. The microarray results revealed that three miRNAs (miR-1260b, miR-423-3p, miR-23a-5p) were differentially expressed in LN metastasis group compared with NLN group. The expression of miR-1260b was tested by qRT-PCR and the mean relative expression fold change (2 -ΔΔCt ) in LN metastasis was significantly higher than that in the NLN group (3.942, 1.743 respectively, P = 1.179E-04). The patients with tumor-node-metastasis (TNM) stage III were identified more frequently in LN metastasis group (P = 1.772E-11) and with a higher expression level of miR-1260b (5.126, P = 1.147E-06). In addition, the LN metastasis cases were associated with a poorly differentiated degree (P = 0.007). The overexpression of miR1260b in NSCLC with LN metastasis can be regarded as a specific signature for early progression and prognosis of NSCLC.
Aim: Overexpression of midkine (MK) has been observed in many malignancies. This aim of this study is to screen for suitable antisense oligonucleotides (ASODN) targeting MK in hepatocellular carcinoma (HCC) cells and evaluate its antitumor activity. Methods: Ten ASODN targeting MK were designed and synthesized. After transfection with ASODN, cell proliferation was analyzed with MTS [3 ‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium, inner salt] assay. In addition, MK mRNA, protein levels, as well as apoptosis and caspase‐3 activity were also examined in HepG2 cells. Cell proliferation was then analyzed after treatment with both ASODN and chemotherapeu‐tic drugs. Results: In this experiment, the ASODN5 among the 10 ASODN showed higher inhibitory activity against proliferation of hepatocellular carcinoma cells in a dose‐dependent manner. In HepG2 cells, ASODN5 could significantly reduce the MK mRNA level and protein content. After transfection with ASODN5 for 48 h, accompanied with a decline of survivin and Bcl‐2 protein content, a remarkable increase of apoptosis and caspase‐3 activity was observed in HepG2 cells. Furthermore, ASODN5 transfer can significantly increase chemosensitivity in HepG2 cells. Conclusion: Antisense oligonucleotides targeting MK shows therapeutic effects on HCC; ASODN5 has the possibility to be developed as an effective antitumor agent.
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