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Background: The importance of N6-methyladenosine (m6A) modification in tumorigenesis and progression have been highlighted. This study aimed to investigate the modification of insulin receptor substrate 1 ( IRS1 ) by m6A and its role in oral squamous cell carcinoma (OSCC)., Methods: Bioinformatics was employed to predict differential genes related to epithelial-mesenchymal transition (EMT) in OSCC. Seventeen pairs of OSCC and paracancerous tissue samples were collected. The impact of IRS1 on OSCC cell growth and EMT was evaluated. The fluctuations in IRS1 enrichment and the involvement of p53/Line-1 were investigated., Results: IRS1 was highly expressed in OSCC. IRS1 silencing decreased OSCC cell proliferation and increased apoptosis. IRS1 silencing hindered EMT by regulating related markers. IRS1 silencing upregulated p53 and downregulated Line-1 ORF1p. The p53 inhibition reversed the effects of IRS1 silencing and induced EMT in OSCC cells. Furthermore, the m6A modification of IRS1 was increased in OSCC cells. IRS1 were positively regulated by the m6A regulators methyltransferase-like 14 (METTL14) and YTH domain-containing protein 1 (YTHDC1). IRS1 bound to YTHDC1, and YTHDC1 knockdown inhibited the IRS1 nuclear export. The obesity-associated protein (FTO) negatively regulated IRS1, and FTO overexpression reversed the IRS1-induced OSCC tumor growth., Conclusions: m6A methylation-mediated IRS1 regulated EMT in OSCC through p53/Line-1. These findings provide potential therapeutic strategies for managing OSCC., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Hyaluronic acid (HA) is a component of the Extra-cellular matrix (ECM), it is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronidase (HAase) is a HA-degrading endoglycosidase, levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1) is the major tumor-derived HAase. We previously demonstrated that HYAL1 were overexpression in human breast cancer. Breast cancer cells with higher HAase expression, exhibited significantly higher invasion ability through matrigel than those cells with lower HAase expression, and knockdown of HYAL1 expression in breast cancer cells resulted in decreased cell growth, adhesion, invasion and angiogenesis. Here, to further elucidate the function of HYAL1 in breast cancer, we investigated the consequences of forcing HYAL1 expression in breast cancer cells by transfection of expression plasmid. Compared with control, HYAL1 up-regulated cells showed increased the HAase activity, and reduced the expression of HA in vitro. Meantime, upregulation of HYAL1 promoted the cell growth, migration, invasion and angiogenesis in vitro. Moreover, in nude mice model, forcing HYAL1 expression induced breast cancer cell xenograft tumor growth and angiogenesis. Interestingly, the HA expression was upregulated by forcing HYAL1 expression in vivo. These findings suggested that HYAL1-HA system is correlated with the malignant behavior of breast cancer.

Aim: To design and synthesize a novel class of antitumor agents, featuring the 3, 5-substituted indolin-2-one framework., Methods: Based on enzyme binding features of (Z)-SU5402, introducing a beta-pyrrole group at the 3-position of the indolin- 2-one core, a series of novel 3,5-substituted indolin-2-ones were designed and synthesized. Four human carcinoma cell lines of A-431, A-549, MDA-MB-468, and Autosomal Dominant Polycystic Kidney disease were chosen for the cell proliferation assay., Results: Twenty new compounds (1a-t) with E configuration have been designed, synthesized and bioassayed. Their structural features were determined by nuclear magnetic resonance (NMR) spectra, low- and high-resolution mass spectra, and confirmed by X-ray crystallography. Although the enzyme assay showed a weak inhibition effect against the epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor tyrosine kinases, the cell-based antitumor activity was promising. Compounds 1 g and 1 h showed higher inhibitory activity toward the A-549 and MDA-MB-468 cell lines with IC(50 ) of 0.065-9.4 micromol/L., Conclusion: This study provides a new template for further development of potent antitumor drugs.

Background & Objective: It is reported that hyaluronidase is related to malignant potentiality of human breast cancer. This study was to investigate whether HYAL1 RNA interference (RNAi) could effectively inhibit gene mRNA expression as well as cell proliferation in human breast cancer cells., Methods: Chemically synthesized double stranded RNA (dsRNA) targeting HYAL1 was transfected into human breast cancer cell lines MDA-MB-231, MDA-MB-453S, ZR-75 and ZR-75-30 using SiPORT lipid. The transfection efficiency was observed under a fluorescence confocal microscopy. Expression of HYAL1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation and cell cycle were determined by MTT and flow cytometry assay, respectively., Results: HYAL1 siRNA effectively inhibited HYAL1 mRNA expression (P<0.05), cell proliferation (P<0.05), and induced cell cycle arrest in G0/G1 phase with a significant decrease of cells in S-phase(P<0.05)., Conclusion: HYAL1-siRNA may be used as a new approach in human breast cancer gene therapy.

Background: Submucosal fibrosis (OSF) of the oral cavity is a chronic scarring disease. Arecoline (Are) is the driving factor for the occurrence and deterioration of OSF. Curcumin plays a vital anti‐inflammatory role in Are‐induced OSF development. However, its potential pharmacological mechanism needs to be elucidated. Methods: The relative molecular level was measured via qRT‐PCR or Western blot. MTT assay, transwell assay and flow cytometry detected cell proliferation, migration, and apoptosis. The correlation between hypoxia‐inducible factor‐1α (HIF‐1α) and LTBP2 promoter was confirmed through dual‐luciferase reporter assay. ELISA was performed to detect inflammatory cytokines levels. Results: Curcumin alleviated Are‐induced oral mucosal fibroblast cells fibrosis by reducing oral mucosa fibroblasts viability, promoting cell apoptosis, suppressing cell migration, and down‐regulating the levels of fibrosis markers and inflammatory factors. Curcumin relieved Are‐induced OSF via inhibiting HIF‐1α. Mechanically, HIF‐1α bound to the promoter of LTBP2 to transcriptionally activated LTBP2. LTBP2 knockdown relieved Are‐induced OSF, and curcumin down‐regulated LTBP2 via inhibiting HIF‐1α to relieve Are‐induced OSF. Moreover, curcumin decreased NF‐κB signal associated proteins via inhibiting LTBP2 to relieve Are‐induced OSF. Conclusion: Curcumin reduced the transcription level of LTBP2 by inhibiting HIF‐1α, thereby inactivating NF‐κB pathway to alleviate Are‐induced OSF. [ABSTRACT FROM AUTHOR]

Objective: To explore the therapeutic effect of naringin on colorectal cancer (CRC) and the related mechanism. Methods: Cell counting kit-8 (CCK-8) assay and annexin V-FITC/PI assay were used to detect the effect of naringin (50–400 µg/mL) on cell proliferation and apoptosis of CRC cells, respectively. The scratch wound assay and transwell migration assay were used to assess the effect of naringin on CRC cell migration. Four-week-old male nude mice were injected with HCT116 cells subcutaneously to establish the tumor xenograft model. Naringin was injected intraperitoneally at 50 mg/(kg·d), with solvent and 5-fluorouracil treatment as control. The width and length of the tumors were measured and recorded every 6 days, and tumor tissues were photographed and weighed on the last day of the 24-d observation period. Immunohistochemical staining for caspase-3, proliferating cell nuclear antigen and TUNEL assay were used to evaluate the effect of naringin on cell proliferation and apoptosis in tumor tissues. The body weight, food and water intake of mice were recorded, and the major organs in different treatment groups were weighed on the last day and stained with hematoxylin and eosin for histological analysis. Meanwhile, the routine blood indicators were recorded. Results: CCK-8 and annexin V-FITC/PI results confirmed that naringin (100, 200, and 400 µg/mL) could inhibit proliferation and promote apoptosis. The scratch wound assay and transwell migration assay results confirmed the inhibitory activity of naringin against CRC cells migration. In vivo results demonstrated the inhibitory effect of naringin on tumor growth with good bio-compatibility. Conclusion: Naringin inhibited colorectal carcinogenesis by inhibiting viability of CRC cells. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) poses a huge threat to women's health. Growing evidence has shown lncRNAs play critical roles in BC progression. However, the effect of LINC00536 in BC remains unknown. LINC00536, miR‐4282, and centromere protein F (CENPF) expressions in BC cells were determined using qPCR assay. Colony formation assay was employed to evaluate the cell proliferation of BC cells. Besides, cell migration and invasion were evaluated using the transwell assay. FISH assay was employed to analyze LINC00536 and miR‐4282 locations in BC cells. Additionally, dual luciferase reporter gene assay was performed to verify the binding relationships between LINC00536 and miR‐4282, miR‐4282 and CENPF. Here, our results displayed that LINC00536 and CENPF were overexpressed in BC cells, while miR‐4282 was downregulated. LINC00536 could negatively regulate miR‐4282 expression via directly binding to miR‐4282. LINC00536 silence suppressed the proliferation, migration, and invasion of BC cells, which was abolished by miR‐4282 inhibition. Additionally, miR‐4282 could negatively regulate CENPF expression via directly binding to CENPF. MiR‐4282 overexpression suppressed BC development, which was abolished by CENPF overexpression. Finally, we proved that LINC00536 silencing suppressed BC growth via regulating the miR‐4282/CENPF axis in vivo. Our research displayed that LINC00536 acted as an oncogene in BC. LINC00536‐enhanced BC cell proliferation, migration, and invasion. Moreover, LINC00536 functioned as a ceRNA to exert malignant characteristics in BC via the miR‐4282–CENPF axis. Collectively, our results demonstrated that the LINC00536–miR‐4282–CENPF axis was a critical player in BC development and was a promising target for BC therapy. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the second most common primary malignant bone tumors in adolescents that causes cancer‐related deaths. Previous studies have confirmed the promoting role of lncRNA HCP5 in the development of OS, but the specific mechanism is still not well understood. MiRNA levels were measured via RT‐qPCR and protein expression was detected via western blotting. Cell proliferation was analyzed by CCK‐8 assays and colony formations assay were conducted to measure colony formation ability. Dual‐luciferase reporter assay was performed to detect the targeting relationship between HCP5 and miR‐29b‐3p, and between miR‐29b‐3p and LOXL2. Wound healing assays and Transwell assays were conducted to verify the migration and invasion abilities of OS cells. Correlations between the levels of HCP5 and miR‐29b‐3p, and between miR‐29b‐3p and LOXL2 were determined by Pearson correlation coefficient analysis. MiR‐29b‐3p expression was decreased and HCP5 and LOXL2 levels were increased in OS tissues and cell lines. MiR‐29b‐3p could directly act on LOXL2 and knockdown of LOXL2 restrained the proliferation, migration, and invasion of OS cells. Moreover, transfection with sh‐HCP5‐1 and sh‐HCP5‐2 suppressed the malignant biological behavior of OS cells. HCP5 directly targeted miR‐29b‐3p, and promoted OS proliferation, migration, and invasion via the miR‐29b‐3p/LOXL2 axis. The lncRNA HCP5 may upregulate LOXL2 expression by targeting miR‐29b‐3p, thereby promoting OS proliferation, migration, and invasion. [ABSTRACT FROM AUTHOR]