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Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Angiogenesis plays a pivotal role in LUAD progression via supplying oxygen and nutrients for cancer cells. Non-coding miR-1293, a significantly up-regulated miRNA in LUAD tissues, can be potentially used as a novel biomarker for predicting the prognosis of LUAD patients. However, little information is available about the function of miR-1293 in LUAD progression especially cancer-induced angiogenesis. Herein, we found that miR-1293 knockdown could obviously attenuate LUAD-induced angiogenesis in vitro and down-regulate two most important pro-angiogenic cytokines VEGF-A and bFGF expression and secretion. Indeed, miR-1293 abrogation inactivated the angiogenesis-promoting ERK1/2 signaling characterized by decreased ERK1/2 phosphorylation and translocation from nucleus to cytoplasm. Next we found that miR-1293 knockdown reactivated the endogenous ERK1/2 pathway inhibitor Spry4 expression and Spry4 perturbance with specific siRNA transfection abolished the inhibition of ERK1/2 pathway and LUAD-induced angiogenesis by miR-1293 knockdown. Finally, with in vivo assay, we found obvious Spry4 up-regulation and VEGF-A, bFGF, ERK1/2 phosphorylation, micro-vessel density marker CD31 expression down-regulation in vivo, respectively. Collectively, these results indicated that miR-1293 knockdown could significantly attenuate LUAD angiogenesis via Spry4-mediated ERK1/2 signaling inhibition, which might be helpful for uncovering more functions of miR-1293 in LUAD and providing experimental basis for possible LUAD therapeutic strategy targeting miR-1293., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood., Methods: The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments., Results: AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells., Conclusions: In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance., (© 2023. The Author(s).)

Due to lack of estrogen receptor α (ERα, gene name: ESR1), ERα-negative breast carcinoma is insensitive to endocrine therapy, and restoration of ERα has become a promising strategy for ERα-negative breast cancer treatment. Sesamol, a naturally occurring phenolic compound, is usually extracted from sesame seeds. Previous investigations have unmasked its anti-oxidant and anti-inflammation properties. In this study, sesamol induced ERα functional re-expression followed by upregulation of its downstream pS2 and GREB1 genes in ERα-negative breast carcinoma. Moreover, it endowed responsiveness of ERα-negative breast carcinoma to the endocrine treatment drug 4-hydroxytamoxifen without influencing the viability of normal human umbilical vein endothelial cells. Mechanistically, sesamol induced ESR1 gene promoter demethylation by downregulating the expression of the DNA methyltransferases DNMT3A and DNMT3B, without affecting DNMT1. Moreover, the non-coding RNA miR-370-3p directly targeted DNMT3A and DNMT3B mRNA, and its expression increased upon treatment with sesamol. Artificial abrogation of miR-370-3p expression with an antagomir abolished the inhibition of DNMT3A and DNMT3B expression by sesamol, resulting in a fallback in ERα reactivation. In mice, sesamol significantly induced ERα re-expression via miR-370-3p-mediated downregulation of DNMT3A and DNMT3B. Sesamol may be a safe and effective option for clinical adjuvant therapy in patients with ERα-negative breast cancer.

The identification of disease-specific alterations in miRNA expression and the ability to detect miRNAs in serum furnish the basis for identified potential research value. This study was aimed to characterize the expression of miRNAs in the serum samples from people with type 2 diabetes mellitus (T2DM) and healthy individuals in order to detect the differential expression of miRNAs in T2DM. In total, 582 participants were recruited. Microarray-based miRNA expression profiles were screened in pooled serum samples from two groups (T2DM and healthy control). The candidates' miRNAs were validated by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Five significantly different serum miRNAs were identified in T2DM patients (hsa-miR-320d, hsa-miR-4534, hsa-miR-3960, hsa-miR-451a, and hsa-miR-572) compared to those in the serum of healthy controls. This study provided evidence that serum miRNAs had differential expressions between healthy controls and T2DM patients. These five differential expression miRNAs might be of help for subsequent study in T2DM.