KMT2A is targeted by miR-361-3p and modulates leukemia cell's abilities to proliferate, migrate and invade.

OBJECTIVE: The lives and safety of humans are significantly threatened by acute myeloid leukemia (AML), which is proven to be the most prevalent acute leukemia. This work is therefore intended to investigate and analyze the expressions of miR-361-3p and Histone Lysine Methyltransferase 2A (KMT2A) in tissues and cell lines of AML and identify an advanced and novel target for the therapy of AML. METHODS: The qRT-PCR and western blot assays were conducted to find expressions of miR-361-3p/KMT2A in AML PB and cell lines. After then, tests using CCK-8 and EdU were run to see how KMT2A affected the growth of AML cells. Transwell migration and invasion assay was conducted to evaluate KMT2A's contribution to the migration and invasion of AML cells. ENCORI and miRWalk predicted the association between KMT2A and miR-361-3p, and the dual-luciferase reporter experiment verified it. Furthermore, rescue studies were used to ascertain how KMT2A affected the miR-361-3p-regulated AML cells' abilities to proliferate, migrate, and invade. RESULTS: miR-361-3p was poorly expressed while KMT2A was abundantly expressed. Additionally, KMT2A downregulation prevented AML cells from proliferating. PCNA and Ki-67 protein levels fell when KMT2A was silent. Furthermore, AML cells' motility, invasion, and metastasis were inhibited by low KMT2A expression. KMT2A was also identified as a direct target of miR-361-3p and negatively correlated with miR-361-3p. Finally, the over-expression of KMT2A partially reversed the inhibitory effects of up-regulation of miR-361-3p. CONCLUSION: A potential therapeutic candidate target for the treatment of AML may be miR-361-3p/KMT2A.

miR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression.

The present study is designed to investigate the expressions of microRNA-143-3p (miR-143-3p) and Lysine acetyltransferase 6A (KAT6A) in acute myeloid leukemia (AML) samples and AML cell lines and to explore the possible effects and underlying mechanisms of miR-143-3p on the proliferation of AML cells. The expressions of miR-143-3p and KAT6A in AML samples and cell lines were detected by RT-qPCR assay. CCK-8 and flow cytometry were performed to evaluate the role of KAT6A in viability of AML cells. EdU assay was performed to determine the effects of KAT6A on proliferation of AML cells. Western blot analysis was utilized to assess the impacts of KAT6A on proliferation-related protein expressions of AML cells. ELISA assay was adopted to illustrate the influence of KAT6A on inflammatory responses of AML cells. In addition, the relationship between KAT6A and miR-143-3p was predicted by ENCORI and miRWalk, and confirmed by dual-luciferase reporter assay. Moreover, the effects of KAT6A on the proliferation of AML cells mediated with miR-143-3p were carried out by rescue experiment. The expression of KAT6A was significantly upregulated, while miR-134-4p was downregulated both in the AML tissues and in AML cell lines. In addition, the silence of KAT6A significantly inhibited the viability of AML cells. Besides, KAT6A silencing notably suppressed the proliferation of AML cells and reduced the protein expressions of Ki-67 and PCNA. Knockdown of KAT6A notably decreased the expression levels of IL-1ß, TNF-α and IL-6, and increased the expression levels of TGF-ß and IL-10. Moreover, overexpression of miR-143-3p repressed viability and proliferation of AML cells and overexpression of KAT6A partially reversed the inhibitory effects of miR-143-3p mimic on viability and proliferation of AML cells. miR-143-3p/KAT6A played an essential role in the viability and proliferation of AML cells.

Early Cranioplasty Benefits Patients with Obvious Bilateral Frontotemporal Bone Window Collapse After Decompressive Craniectomy.

OBJECTIVE: Obvious skin flap collapse is often accompanied by reduced neurologic recovery after decompressive craniectomy. This study explored the feasibility of early cranioplasty (EC) in patients with obvious bilateral frontotemporal bone window (BFBW) collapse after decompressive craniectomy. METHODS: Patients with obvious BFBW collapse who underwent EC or traditional cranioplasty (TC) were divided into 3 groups according to their preoperative Glasgow Coma Scale (GCS) scores. The indexes, including postoperative incision healing, salivation symptoms, postoperative infection, and 6-month postoperative follow-up after EC or TC, were compared in each group. RESULTS: Two of 32 patients with GCS scores of 3 to 8 points experienced poor healing of the scalp incision after EC, whereas no TC patients had poor healing. Incision healing significantly differed between these 2 groups (P > 0.05), and long-term prognoses based on GOS scores were the same after a 6-month postoperative follow-up (P > 0.05). In patients with GCS scores of 9 to 12 points, salivation improved by 84.2% and 17.6% in the EC and TC groups, respectively (P < 0.05) after a mean follow-up time of 6 months. Similarly, positive neurologic recovery rates (GOS score 4-5 points) were higher in the EC group (88.9%) than in the TC group (60.0%) (P < 0.05) and did not differ between the EC (79.3%) and TC (80.6%) groups in patients with GCS scores of 13 to 15 points (P > 0.05). However, salivation improved by 86.7% in the EC group but by only 12.5% in the TC group (P < 0.05). CONCLUSION: We therefore recommend EC for patients with obvious BFBW collapse and GCS scores ≥9.