GINS subunit complex 4 (GINS4) is fundamental to DNA replication and G1/S phase transition of the cell cycle in eukaryotes. Further, recent studies implied that GINS4 can mediate the progression of several tumors, but its mechanism in lung adenocarcinoma (LUAD) is not clarified. Therefore, the role of GINS4 in LUAD was explored. miR-133a-3p and GINS4 mRNA expression were tested through qRT-PCR. Protein levels of the two genes were assayed by Western blot. Their targeting relationship was predicted and verified by bioinformatics prediction and dual-luciferase analysis. The functions of miR-133a-3p and GINS4 in LUAD were evaluated by Transwell, wound healing, CCK-8, and flow cytometry assays. MTT assay and caspase-3 activity detection were utilized to measure the regulation of miR-133a-3p/GINS4 in the cisplatin sensitivity of LUAD cells. The results showed that GINS4 was highly expressed in LUAD cells (p < 0.05). miR-133a-3p, the upstream gene of GINS4 in LUAD, negatively mediated GINS4 expression. Moreover, overexpressing GINS4 enhanced the proliferative, migratory, and invasive abilities of LUAD cells and inhibited cell apoptosis and the sensitivity to cisplatin, while overexpressing miR-133a-3p caused the contrary results. However, the promoting effects of GINS4 overexpression on LUAD could be offset by miR-133a-3p overexpression. miR-133a-3p could regulate malignant behaviors and cisplatin sensitivity of LUAD cells through negatively regulating GINS4. In conclusion, our findings demonstrated that GINS4 was overexpressed in LUAD and promoted the malignant behavior of LUAD cells. Moreover, miR-133a-3p could negatively regulate GINS4, thereby suppressing the malignant progression and increasing the cisplatin sensitivity of LUAD
Asthma has significant impacts on living quality particularly in children. Long noncoding RNA (lncRNA) MALAT1 plays a crucial role in neonatal respiratory diseases. Meanwhile, MALAT1 knockdown could induce viability and attenuate apoptosis of airway-related cells. However, the role of MALAT1 in neonatal asthma, asthma-related cell, and its possible mechanism is unclear. This study aims to investigate MALAT1 level in asthma and to identify the effects of MALAT1 on bronchial/tracheal smooth muscle cells (B/TSMCs). Newborn asthma modeling rat was constructed by introducing ovalbumin (OVA). MALAT1 levels in tissues or B/TSMCs were determined by RT-qPCR. Exogenous changes of MALAT1, RyR2 or miR-133a in B/TSMCs were fulfilled by cell transfection; cell apoptosis was measured by using Cell Death Detection ELISA kit and Hochest33342; IL-6, TNF-α and IL-1β level was detected by using corresponding ELISA kit; ryanodine receptor 2 (RyR2) mRNA and miR-133a level was determined by RT-qPCR; cleaved caspase-3 (c-caspase-3) and RyR2 expression was detected by Western blot; luciferase reporter assay was performed to confirm the target regulation of miR-133a on RyR2. We found that MALAT1 was significantly upregulated in tracheal tissues of newborn asthma modeling rats. In MALAT1-silenced or -overexpressed B/TSMCs, we found a synchronous change of cell apoptosis, inflammatory factor secretion (IL-6, TNF-α, and IL-1β) or RyR2 level, but a reverse change of miR-133a level with MALAT1. Besides, MALAT1 induced B/TSMCs apoptosis and inflammation increase could be partially reversed when RyR2 was silenced or when miR-133a was overexpressed. The luciferase reporter assay confirmed that RyR2 is a direct target gene of miR-133a in B/TSMCs. Finally, we conclude that MALAT1 knockdown could protect from B/TSMCs injury via regulating miR-133a/RyR2 axis.
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