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Angiogenesis is a significant character of lung adenocarcinoma (LUAD) and is an important reason leading to high mortality rates of LUAD patients. However, the molecular mechanisms of lncRNAs regulating the angiogenesis in LUAD have not been fully elucidated. Here we show lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis. Mechanistically, CAR10 could bind to Lactate Dehydrogenase A (LDHA) protein to regulate the phosphorylation and acetylation of LDHA and increase the dimerization of LDHA to promote its nuclear translocation, which increased the H3K79 methylation in Vascular Endothelial Growth Factor A (VEGFA) and Vascular Endothelial Growth Factor C (VEGFC) gene interval. CAR10 induced microvascular formation in vivo and in vitro by regulating LDHA-VEGFA/C axis. In addition, MYC and TP53 bonded to the promotor of CAR10 and reverse regulated its expression in LUAD cells. CAR10 regulates post-translational modification of LDHA and increases the H3K79 methylation of VEGFA/VEGFC to promote angiogenesis of LUAD, which is a potential therapeutic target for LUAD. Long non-coding RNA CAR10 regulates post-translational modification of LDHA and increases the H3K79 methylation of VEGFA/VEGFC to promote angiogenesis of lung adenocarcinoma, which is a potential therapeutic target for lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective: Wilm’s tumor is a common renal malignancy in childhood with unsatisfactory prognosis. microRNA-215-5p (miR-215-5p) has been reported as a tumor-suppressive miRNA in different types of human cancers, but rarely in the Wilm’s tumor. In light of this, we tried to investigate the regulatory role and underlying mechanism of miR-215-5p in the Wilm’s tumor. Methods: After sample collection and cell culture, the expression of miR-215-5p and CT10 Regulator of Kinase (CRK) was detected. Then rhabdoid tumor cell lines (formerly classified as Wilms’ tumor cell lines), G401 and WT-CLS1 cells were transfected with pcDNA3.1, pcDNA3.1-CRK, sh-NC, sh-CRK, agomir NC, miR-215-5p agomir, antagomir NC or miR-215-5p antagomir to explore the function of miR-215-5p and CRK in the Wilm’s tumor cell proliferation and migration. Moreover, the relationship between miR-215-5p and CRK was analyzed by dual luciferase reporter gene assay. Results: Lowly-expressed miR-215-5p and highly-expressed CRK were observed in the Wilm’s tumor tissues and cells. Transfection of pcDNA3.1-CRK or miR-215-5p antagomir could promote G401 and WT-CLS1 cell proliferation and enhance migration ability, while transfection of sh-CRK or miR-215-5p agomir led to opposite results. Additionally, miR-215-5p may bind to CRK. Moreover, transfection of pcDNA3.1-CRK in G401 and WT-CLS1 cells could partially reverse the inhibitory effect of miR-215-5p agomir on the proliferation and migration of Wilm’s tumor cells. Conclusion: Our study highlighted that miR-215-5p could suppress the proliferation and migration of Wilm’s tumor cells by regulating the expression of CRK, providing new ideas for molecular targeted therapy for Wilm’s tumor.

Background: As a primary chemotherapeutic agent for lung adenocarcinoma (LUAD), pemetrexed (PEM) faces the challenge of resistance development in cancer cells due to its chronic use, which compromises its therapeutic benefits. LncRNA-NEAT1, implicated in the promotion of cancer, is a key player in LUAD. The objective of this study is to explore the contribution of lncRNA-NEAT1 to PEM resistance in LUAD and to dissect the molecular mechanisms involved. Method: The expression levels of lncRNA-NEAT1 in LUAD tissues and cells were deciphered using the TCGA database and qRT-PCR. To delve into the functional implications of lncRNA-NEAT1, we engineered plasmids to modulate its expression levels in PEM-resistant A549 cells. PEM resistance in the modified cells was then quantitatively assessed via a panel of assays including cell counting kit-8 (CCK-8), and colony formation, and flow cytometry. To predict the interaction sites between lncRNA-NEAT1 and miR-379-3p, along with the miR-379-3p and hypoxia-inducible factor (HIF1A), we referred to the StarBase and TargetScan databases. The interplay between these RNA molecules was further characterized by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays, while the expression of autophagy-related proteins LC3I, LC3II, and Beclin1 was profiled using western blot (WB). Results: Abundant lncRNA-NEAT1 expression was observed in LUAD tissues and cell lines. Its depletion resulted in impeded growth of A549/PEM cells, enhanced apoptotic rates, and a lowered threshold for PEM to exert a half-maximal inhibitory effect. The interplay between lncRNA-NEAT1 and miR-379-3p, as evidenced by dual-luciferase reporter assays, RIP, and qRT-PCR, led to the upregulation of HIF1A. WB and CCK-8 outcomes illustrated that the autophagy and PEM resistance were compromised when HIF1A expression was curtailed by miR-379-3p mimics in A549/PEM cells. The restoration of these effects was observed upon lncRNA-NEAT1-mediated downregulation of miR-379-3p. Conclusion: Our study illuminates the role of lncRNA-NEAT1 in LUAD, where it mediates resistance to PEM through the activation of autophagy via the miR-379-3p/HIF1A axis. This work paves the way for new therapeutic strategies for managing PEM resistance in LUAD patients. [ABSTRACT FROM AUTHOR]

Objective: Aberrant miR-129-5p expression is a key modulator of cancer development. But how the miRNA affects colorectal cancer (CRC) remains unclear. This study was designed to illustrate the underlying mechanism of miR-129-5p in CRC., Methods: MiR-129-5p expression at cellular level was assayed by qRT-PCR. Its role in CRC cell phenotypes was studied by cell function experiments. The binding relationship between miR-129-5p and TRIP13 was analyzed and verified by target changed to bioinformatics prediction and dual-luciferase detection. Furthermore, the functional mechanism based on miR-129-5p and TRIP13 in CRC was studied through rescue experiments., Results: CRC cell lines presented prominently lower miR-129-5p levels than the normal colon epithelial cell line. The forced miR-129-5p level suppressed CRC cell growth. TRIP13 was proved to be a target of miR-129-5p in CRC cells, and miR-129-5p overexpression reduced TRIP13 expression. TRIP13 knockdown resulted in cell cycle arrest. Additionally, TRIP13 overexpression restored the impacts of miR-129-5p overexpression on cell malignant phenotypes and cell cycle., Conclusion: MiR-129-5p down-regulated TRIP13 expression, thereby restraining the malignant progression of CRC cells. The findings may offer a new target for molecular therapy of CRC., (©The Author(s) 2022. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Objective: To formulate the classification criteria of femoral intertrochanteric fractures based on irreducibility or not in order to predict the difficulty of fracture recovery., Methods: A clinical data of 244 patients with closed femoral intertrochanteric fractures admitted between January 2017 and March 2020 was retrospectively analyzed. There were 116 males and 128 females with an average age of 77.9 years (range, 45-100 years). The cause of injury included falling in 190 cases, traffic accident in 36 cases, smashing in 13 cases, and falling from height in 5 cases. The time from injury to operation was 1-14 days (mean, 3.6 days). According toAO/Orthopaedic Trauma Association (AO/OTA) classification, the fractures were classified as type 31-A1 in 38 cases, type 31-A2 in 160 cases, and type 31-A3 in 46 cases. According to whether the recovery difficulty occurred after intraoperative closed traction reset, the patients were divided into reducible-group and irreducible-group; combined with the literature and preoperative imaging data of two groups, the classification criteria of femoral intertrochanteric fractures was formulated based on the irreducibility or not. The 244 fractures were classified by the doctors who did not attend the operation according to the classification criteria, predicted the difficulty of fracture reduction, and compared with the actual intraoperative reduction situation., Results: The 244 patients were divided into reducible-group ( n =164, 67.21%) and irreducible-group ( n =80, 32.79%) according to the intraoperative difficulty of reduction. Comparing the imaging data and characteristics of the two groups, and formulating the classification criteria of femoral intertrochanteric fractures based on irreducibility or not, the fractures were mainly divided into two categories of irreducibility and reducibility. The fractures of irreducibility category was divided into typesⅠ-Ⅴ, among which type Ⅲ was divided into subtypes 1-4; the fractures of reducibility category was divided into typesⅠand Ⅱ. Compared with the actual intraoperative evaluation results, the total accuracy rate of the doctors who did not attend the operation was 81.15% (198/244) based on the classification criteria of femoral intertrochanteric fractures. The accuracy rate of irreducibility category was 65.74% (71/108), and the reducibility category was 93.38% (127/136). All patients were followed up 13-25 months, with an average of 17.6 months. All fractures healed except 2 cases died of infection., Conclusion: The classification criteria of femoral intertrochanteric fractures based on irreducibility or not can accurately predict the reducible cases preoperatively, and most of the irreducible cases can be correctly predicted in a wider way. But the classification criteria still need to be further improved and supplemented.

Objective To explore whether oncolytic adenovirus expressing CCL19 can inhibit the growth of gastric cancer cells and activate anti-tumor immune response. Methods Mouse CCL19 gene was inserted into the E3 region of oncolytic adenovirus Ad5 to obtain engineered oncolytic adenovirus Ad5-CCL19. The expression of CCL19 in Ad5-CCL19-infected mouse MFC cells was detected by Western blotting. The effects of Ad5-CCL19 on the proliferation of MFC cells, MGC803 cells and BGC823 cells were tested by MTT assay. The anti-tumor activity of Ad5-CCL19 in vivo was examined by MFC cell subcutaneous transplantation tumor model. Immunofluorescence histochemical staining was used to detect CD4 and CD8 expression in tumor tissue. The secretion levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in tumor infiltrating T cells were detected by flow cytometry. Results Ad5-CCL19 could effectively infect MFC cells to secrete CCL19. Also, Ad5-CCL19 could induce significant dose-dependent cytotoxicity against target cells in vitro. The experiment in vivo showed that Ad5-CCL19 had stronger inhibitory effects on MFC cell tumor than Ad5 in the mice, and it could effectively enhance the infiltration of CD4 + T cells and CD8 + T cells and increase the secretion of IFN-γ and TNF-α in tumor tissues. Conclusion Ad5-CCL19 can significantly infect MFC gastric cancer cells to inhibit their growth and improve the anti-tumor immune activity of the tumor site.