MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling

Huang

2020

Aging

We investigated the influence of the long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) on the malignant phenotype of non-small cell lung cancer (NSCLC) cells in vitro and in vivo. We also explored the mechanisms by which VPS9D1-AS1 exerts its oncogenic action during NSCLC progression. VPS9D1-AS1 expression was upregulated in NSCLC; the extent of its upregulation significantly correlated with patients' adverse clinicopathological characteristics and shorter overall survival. When VPS9D1-AS1 was knocked down in NSCLC cells, their proliferation, colony-forming capacity, migration, and invasiveness were lower, whereas their apoptosis rate was higher, compared to the control. VPS9D1-AS1 knockdown attenuated tumor growth of NSCLC cells in vivo. Mechanistically, VPS9D1-AS1 directly interacted with microRNA-532-3p (miR-532-3p) in NSCLC cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR-532-3p inhibition. Furthermore, VPS9D1-AS1 knockdown decreased the expression of high mobility group AThook 2 (HMGA2) in NSCLC cells via miR-532-3p sponging. Recovery of HMGA2 expression partially reversed the inhibitory effects of VPS9D1-AS1 knockdown on NSCLC cells. Thus, VPS9D1-AS1 functions as a competing endogenous RNA that positively regulates HMGA2 expression by sponging miR-532-3p in NSCLC cells, suggesting that the VPS9D1-AS1-miR-532-3p-HMGA2 pathway can be a potential diagnostic and/or therapeutic target in NSCLC.

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression

Huang

2020

Aging

“…The downregulation of miR-129-5p and miR-532-3p are associated with the poor prognosis in manifold cancer types, which are involved in the EMT program [114][115][116][117]. Hence, Luan et al and Gu et al used miR-129-5p and miR-532-3p mimics, respectively, to enhance the chemosensitivity in vivo [118,119]. Recently, miR-147, miR-335, miR-1976, and miR-4319 were identified as tumor suppressor miRNAs for inhibiting EMT and CSCs simultaneously [120][121][122][123].…”

Section: Mirnas Inhibit Cscs To Overcome Chemotherapy Resistancementioning

confidence: 99%

MiRNA-mediated EMT and CSCs in cancer chemoresistance

Dong

Zhu

et al. 2021

Exp Hematol Oncol

Cancer stem cells (CSCs) are a small group of cancer cells, which contribute to tumorigenesis and cancer progression. Cancer cells undergoing epithelial-to-mesenchymal transition (EMT) acquire the chemoresistant ability, which is regarded as an important feature of CSCs. Thus, there emerges an opinion that the generation of CSCs is considered to be driven by EMT. In this complex process, microRNAs (miRNAs) are found to play a key role. In order to overcome the drug resistance, inhibiting EMT as well as CSCs phenotype seem feasible. Thereinto, regulating the EMT- or CSCs-associated miRNAs is a crucial approach. Herein, we conduct this review to elaborate on the complicated interplay between EMT and CSCs in cancer chemoresistance, which is modulated by miRNAs. In addition, we elucidate the therapeutic strategy to overcome drug resistance through targeting EMT and CSCs.

“…Moreover, inhibition of EMT is also a common feature observed for miRs that sensitize resistant colon cancer cell lines to 5-FU and L-OHP. As we previously mentioned, upregulation of miR-125b-5p, miR-195-5p, miR-139-5p, miR-324-5p, miR-320, and miR-532-5p have shown to inhibit the EMT process in colon cancer cells, leading to the acquisition of an epithelial phenotype, and restoring sensitivity to 5-FU and L-OHP in vitro [ 44 , 51 , 53 , 54 , 56 ]. Downregulation of FOXM1 by miRs also leads to inhibition of EMT and suppression of invasive phenotype in colon cancer cell lines, combined with restoration of chemosensitivity [ 47 , 69 ].…”

Section: Mir Biogenesis and Cancermentioning

confidence: 99%

Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX

2021

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.