MIR-140 TARGETS LNCRNA DNAJC3-AS1 TO SUPPRESS CELL PROLIFERATION IN ACUTE MYELOID LEUKEMIA

Objectives：MiR-140 and DNAJC3-AS1 have been proven to play critical roles in cancer biology, while their participations in acute myeloid leukemia (AML) are unclear. This study aimed to explore the role of miR-140 and DNAJC3-AS1 in AML. Methods：Analysis of the expression of DNAJC3-AS1 and miR-140 was done with RT-qPCR. The role of DNAJC3-AS1 and miR-140 in the expression of each other was explored with overexpression assay. The direct interaction between DNAJC3-AS1 and miR-140 was analyzed with RNA pull-down assay. The subcellular location of DNAJC3-AS1 was explored with cellular subcellular fractionation assay. Cell proliferation analysis was done with BrdU assay. Results：AML patients showed increased expression of DNAJC3-AS1 and decreased expression of miR-140. DNAJC3-AS1 was detected in both nuclear and cytoplasm samples, and a direct interaction between DNAJC3-AS1 and miR-140 was observed. Discussion：Reduced expression of DNAJC3-AS1 was observed after miR-140 overexpression in AML cells. DNAJC3-AS1 increased cell proliferation and inhibited the role of miR-140 in suppressing cell proliferation. Conclusion：In conclusion, miR-140 may target DNAJC3-AS1 to suppress cell proliferation in AML.

Circular RNA circRHOBTB3 is downregulated in hepatocellular carcinoma and suppresses cell proliferation by inhibiting miR-18a maturation

Background Circular RNA circRHOBTB3 has been characterized as a tumor suppressor in gastric cancer, while its role in hepatocellular carcinoma (HCC) is unknown. This study was carried out to analyze the role of circRHOBTB3 in HCC. Methods In this study, circRHOBTB3, mature miR-18a, and miR-18a precursor in HCC and paired non-cancer tissues were detected by RT-qPCR. The role of circRHOBTB3 in the production of mature miR-18a was explored by transfecting circRHOBTB3 expression vector into HCC cells, followed by RT-qPCR to determine the expression of mature miR-18a and miR-18a precursor. The role of circRHOBTB3 and miR-18a in HCC cell proliferation was studied using CCK-8 assay. Results CircRHOBTB3 was under-expressed in HCC compared to normal tissues. In HCC cells, circRHOBTB3 overexpression decreased mature miR-18a level but not miR-18a precursor. Cell proliferation analysis showed that circRHOBTB3 overexpression decreased cell proliferation while miR-18a overexpression increased cell proliferation. Moreover, circRHOBTB3 suppressed the role of miR-18a in cell proliferation. Conclusions CircRHOBTB3 is downregulated in HCC and may suppress cell proliferation by reducing miR-18a production.

MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3′UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

Bifunctional Aptamer Drug Carrier Enabling Selective and Efficient Incorporation of an Approved Anticancer Drug Irinotecan to Fibrin Gels

We have previously developed a bifunctional aptamer (bApt) binding to both human thrombin and camptothecin derivative (CPT1), and showed that bApt acts as a drug carrier under the phenomenon named selective oligonucleotide entrapment in fibrin polymers (SOEF), which enables efficient enrichment of CPT1 into fibrin gels, resulting in significant inhibition of tumor cell growth. However, although the derivative CPT1 exhibits anticancer activity, it is not an approved drug. In this study, we evaluated the binding properties of bApt to irinotecan, a camptothecin analog commonly used for anticancer drug therapy, in addition to unmodified camptothecin (CPT). Furthermore, we have revealed that irinotecan binds to bApt like CPT1 and is selectively concentrated on fibrin gels formed around the tumor cells under the SOEF phenomenon to suppress cell proliferation.