Ginkgolic Acid (GA) Inhibits the Growth of OCa by Inhibiting lncRNA MALAT1/JAK2 Axis

Objective. We aimed to observe the impact of ginkgolic acid (GA) on the proliferation and metastasis ability of ovarian cancer (OCa) cells and to further explore whether GA affects the malignant progress of OCa via regulating the lncRNA MALAT1/JAK2 axis. Methods. OCa cells SKOV3 and CAOV3 were administered with 1 ng/ml GA, 5 ng/ml GA, 10 ng/ml GA, 20 ng/ml GA, and DSMO as control, respectively. The cell proliferation and migration ability of the abovementioned cells in each group were measured by CCK-8 test and Transwell experiments. The expression levels of lncRNA MALAT1 and JAK2 protein were examined by qRT-PCR and western blot, respectively. Subsequently, in OCa cells treated with GA, lncRNA MALAT1 overexpression vector was transfected to continue to detect the proliferation activity and migration ability of each treatment group. Finally, the regulation of GA on activity of lncRNA MALAT1/JAK2 axis in OCa cells was further explored in nude mice. Results. Our data showed that the proliferation inhibition rate of cells at each ginkgolic acid concentration was higher than that of the control group ( P < 0.05 ), suggesting that GA has an inhibitory influence on the proliferation of OCa cells, in a dose-dependent way. GA was able to inhibit the proliferation rate and migration ability of OCa cells. Administration of ginkgolic acid downregulated the levels of lncRNA MALAT1 and JAK2 protein. Overexpression of lncRNA MALAT1 partially reversed the inhibited OCa proliferative capacity caused by GA treatment. Consistent with the results observed in vitro, we also found that the OCa tumor weight and volume of nude mice injected with lncRNA MALAT1 overexpression vector were enhanced and JAK2 protein level increased remarkably in comparison to the ginkgolic acid group. Conclusions. In summary, GA may exert its inhibitory effect on the proliferative and migratory capacities of OCa cells through suppressing the activity of lncRNA MALAT1/JAK2 axis.

LncRNA MALAT1 Modulates TGF-β1-Induced EMT in Keratinocyte

One of the major complications in diabetes is impaired wound healing. Unfortunately, effective therapies are currently lacking. Epithelial to mesenchymal transition (EMT) is a critical process involved in cutaneous wound healing. In response to injury, EMT is required to activate and mobilize stationary keratinocytes in the skin toward the wound bed, which allows for re-epithelialization. This process is stalled in diabetic wounds. In this study, we investigate the role of long non-coding RNA (lncRNA), MALAT1, in transforming growth factor beta 1(TGF-β1)-induced EMT of human keratinocyte (HaCaT) cells. Initially, we detected MALAT1 and TGF-β1 expression in non-diabetic and diabetic wounds and found that these expression are significantly up-regulated in diabetic wounds. Then, HaCaT cells were cultured and exposed to TGF-β1. The EMT of HaCaT cells were confirmed by the increased expression of CDH2, KRT10, and ACTA2, in addition to the down-regulation of CDH1. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). MALAT1 silencing attenuates TGFβ1-induced EMT. Mechanistically, MALAT1 is involved in TGF-β1 mediated EMT through significantly induced ZEB1 expression, a critical transcription factor for EMT. In summary, lncRNA MALAT1 is involved in TGFβ1-induced EMT of human HaCaT cells and provides new understanding for the pathogenesis of diabetic wounds.

lncRNA MALAT1 Mediates Osteogenic Differentiation and Apoptosis in Osteoporosis by Regulating the miR-485-5p/WNT7B Axis

Background: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis. This study aimed to investigate the effects of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on osteogenic differentiation and cell apoptosis in osteoporosis. Methods: hindlimb unloading (HU) was performed to establish osteoporosis model in vivo. MicroCT was applied for pathological analysis. Microgravity (MG) was used to construct osteoporosis in vitro. The mRNA and miRNA expression was determined using RT-qPCR. Protein expression was determined using western blot. The binding sites between miR-485-5p and MALAT1/Wnt family member 7B (WNT7B) was predicted by bioinformatics analysis and verified by luciferase and RNA pull-down assays. Cellular functions were determined by ALP staining, Alizarin red staining, and flow cytometry assays. Results: MALAT1 expression was downregulated in HU mice and MG treated MC3T3-E1 cells. However, overexpression of MALAT1 upregulated the expression of Bmp4, Col1a1, Spp1, and enhanced ALP activity. Additionally, overexpression of MALAT1 inhibited apoptosis, decreased Bax and caspase-3 levels, and increased Bcl-2 level. Moreover, MALAT1 overexpression improved bone phenotype in vivo. MALAT1 functioned as a ceRNA to upregulate WNT7B. Overexpression of miR-485-5p rescued the promotion of osteogenic differentiation and the inhibition of apoptosis induced by MALAT1. Knockdown of WNT7B abolished the facilitation of osteogenic differentiation and the suppression of apoptosis induced by downregulation of miR-485-5p. Conclusion: In conclusion, MALAT1 promoted osteogenic differentiation and inhibited cell apoptosis through miR-485-5p/WNT7B axis, which suggested that MALAT1 is a potential target to alleviate osteoporosis.