Lung cancer is the most common cause of cancer‐related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2‐MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression of MCM4 (P = 0.0032), MCM5 (P = 0.0032), and MCM7 (P = 0.0110) significantly predicted 5‐year survival rates in patients with LUAD. Simurosertib (TAK‐931) significantly suppressed the proliferation of LUAD cells by inhibiting cell division cycle 7‐mediated MCM2 phosphorylation. This finding suggested that MCM2 might be a therapeutic target for LUAD. Moreover, analysis of the epigenetic regulation of MCM2 showed that miR‐139‐3p, miR‐378a‐5p, and miR‐2110 modulated MCM2 expression in LUAD cells. In patients with LUAD, understanding the role of these miRNAs may improve prognoses.
Background:The da Vinci Si version of robot lacks a vascular stapler that can be controlled by the operating surgeon at the surgical console for dividing the pulmonary vessels. Therefore, in order to initiate and safely perform robotic anatomical lobectomy for lung cancer, it is important to develop a safe method for introducing the surgical stapler.
Method:We performed a retrospective study of the first 42 consecutive patients who underwent robotic lobectomy for lung cancer at Nippon Medical School Hospital between January 2019 and December 2020.
Results:Up to case 18, we performed Robot-assisted thoracoscopic surgery (RATS) lobectomy using the four-arm approach with two assistant ports. For dividing the pulmonary vessels, the surgical stapler was introduced through the assist ports. However, since this is not the port position usually used in video-assisted thoracoscopic surgery (VATS), there were many difficult situations.3 From case 19 onwards of RATS lobectomy, we began to use a total port approach using three robotic arms and two assistant ports. For resecting the pulmonary vessels or bronchi with endoscopic staplers, the port for the robotic arm was removed and the endoscopic staplers were placed through a 12-mm Xcel bladeless port. This change resulted in a shorter operation time, less blood loss, and less robotic arm interference. There has been no case that developed intraoperative complications during RATS lobectomy.
Conclusion:The new total port approach, with three robotic arms, for introducing surgical staplers during RATS using the da Vinci Si robotic system appears to be feasible.
The involvement of passenger strands of miRNAs in the molecular pathogenesis of human cancers is a recent concept in miRNA research, and it will broaden our understanding of the molecular mechanisms of miRNA-mediated cancer. The analysis of our miRNA signature of LUAD revealed that both strands of pre-miR-486 (miR-486-5p and miR-486-3p) were downregulated in LUAD tissues. Ectopic expression of both miRNAs induced cell cycle arrest in LUAD cells, suggesting both strands of miRNAs derived from pre-miR-486 were tumor suppressive. Our in silico analysis showed a total of 99 genes may be under the control of both miRNAs in LUAD cells. Importantly, among these targets, the high expression of seven genes (MKI67, GINS4, RRM2, HELLS, MELK, TIMELESS, and SAPCD2) predicted a poorer prognosis of LUAD patients (p < 0.05). We focused on GINS4, a DNA replication complex GINS protein that plays an essential role in the initiation of DNA replication. Our functional assays showed that GINS4 was directly controlled by both strands of pre-miR-486, and its aberrant expression facilitated the aggressive behavior of LUAD cells. GINS4 is attractive as a therapeutic target for this disease. MiRNA analysis, including passenger strands, will further improve our understanding of the molecular pathogenesis of LUAD.
Cholinergic receptor muscarinic 3 (CHRM3)‐mediated focal adhesion kinase/YES‐associated protein (YAP) signalling is essential for the growth of castration‐resistant prostate cancer (CRPC) cells. Here, we evaluated the molecular mechanisms through which CHRM3 overexpression facilitates castration‐resistant growth. Small RNA sequencing combined with in silico analyses revealed that CHRM3 was a putative target of miR‐15b‐5p. Notably, androgen deprivation suppressed miR‐15b‐5p expression and increased CHRM3 expression. Moreover, miR‐15b‐5p bound directly to CHRM3 and inhibited YAP activation induced by CHRM3 stimulation. Furthermore, miR‐15b‐5p abolished the growth of CRPC cells induced by CHRM3 stimulation. We conclude that the miR‐15b‐5p/CHRM3/YAP signalling axis promotes the castration‐resistant growth of prostate cancer.
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