MiR-579 Inhibits Lung Adenocarcinoma Cell Proliferation and Metastasis via Binding to CRABP2

Yi, Qijun; Miao, Yu-e; Kong, Ying; Xu, Yan; Zhou, Jinghao; Dong, Qi; Liu, Haiyan

doi:10.1155/2022/9111681

Cited by 5 publications

(6 citation statements)

References 25 publications

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“…Indeed, besides the effects on BRAF oncogenic signaling, miR-579-3p is also able to target MDM2 oncoprotein [ 13 ] which is fundamental to sustain anti-apoptotic signals responsible for drug tolerant/resistant states [ 40 ]. In line with our findings, miR-579-3p oncosuppressive role has been also described in other solid tumors, like lung and hepatocellular adenocarcinomas [ 41 , 42 ].…”

Section: Discussionsupporting

confidence: 91%

The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors

Liguoro,

Frigerio,

Ortolano

et al. 2024

Cell Death Dis

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Therapy of melanoma has improved dramatically over the last years thanks to the development of targeted therapies (MAPKi) and immunotherapies. However, drug resistance continues to limit the efficacy of these therapies. Our research group has provided robust evidence as to the involvement of a set of microRNAs in the development of resistance to target therapy in BRAF-mutated melanomas. Among them, a pivotal role is played by the oncosuppressor miR-579-3p. Here we show that miR-579-3p and the microphthalmia-associated transcription factor (MITF) influence reciprocally their expression through positive feedback regulatory loops. In particular we show that miR-579-3p is specifically deregulated in BRAF-mutant melanomas and that its expression levels mirror those of MITF. Luciferase and ChIP studies show that MITF is a positive regulator of miR-579-3p, which is located in the intron 11 of the human gene ZFR (Zink-finger recombinase) and is co-transcribed with its host gene. Moreover, miR-579-3p, by targeting BRAF, is able to stabilize MITF protein thus inducing its own transcription. From biological points of view, early exposure to MAPKi or, alternatively miR-579-3p transfection, induce block of proliferation and trigger senescence programs in BRAF-mutant melanoma cells. Finally, the long-term development of resistance to MAPKi is able to select cells characterized by the loss of both miR-579-3p and MITF and the same down-regulation is also present in patients relapsing after treatments. Altogether these findings suggest that miR-579-3p/MITF interplay potentially governs the balance between proliferation, senescence and resistance to therapies in BRAF-mutant melanomas.

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Section: Discussionsupporting

confidence: 91%

The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors

Liguoro,

Frigerio,

Ortolano

et al. 2024

Cell Death Dis

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“…In addition, CRABP2 can interact with HuR, enhancing the binding ability of HuR to target RNA and increasing RNA stability [ 13 ]. Currently, abnormal expression of CRABP2 has been found in various tumors [ 14 – 17 ], either upregulated or downregulated, and its role in tumors is not yet clear. The expression of CRABP2 in breast cancer tissues is significantly up-regulated, and it may become a new diagnostic marker for breast cancer [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α

Fu,

Zhang,

Wang

et al. 2024

Cell Death Dis

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Ovarian cancer is the most lethal malignancy among gynecologic cancers, and primary and secondary chemotherapy resistance is one of the important reasons for poor prognosis of ovarian cancer patients. However, the specifics of resistance to chemotherapy in ovarian cancer remain unclear. Herein, we find that the expression level of cellular retinoic acid binding protein 2 (CRABP2) is up-regulated in drug-resistant ovarian cancer tissues and cell lines, and the expression levels of CRABP2 in epithelial ovarian cancer tissues are closely related to tumor clinical stage and patients’ prognosis, suggesting that CRABP2 plays an important role in the progression of ovarian cancer and the corresponding ability of tumor to chemotherapy. With the in-depth study, we demonstrates that CRABP2 is related to the high metabolic activity in drug-resistant cells, and all-trans retinoic acid exacerbates this activity. Further molecular mechanism exploration experiments show that CRABP2 not only up-regulates the expression level of HIF1α, but also increases the localization of HIF1α in the nucleus. In drug-resistant ovarian cancer cells, knocking down HIF1α can block the resistance of CRABP2 to chemotherapy drugs in ovarian cancer cells. Taken together, our findings suggest for the first time that CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α. This study provides a possible molecular mechanism for drug resistance and a possible molecular target for clinical treatment of ovarian cancer.

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“…Alterations in the Wnt/β-catenin pathway contribute to the development/progression of several types of cancer, including NSCLC (17). Numerous studies have demonstrated the dysregulation of miRNAs in several types of cancer (18)(19)(20), and that aberrantly expressed miRNAs are related to dysregulation of the Wnt/β-catenin signaling (6). Numerous miRNAs inactivate the Wnt/β-catenin signaling pathway to affect the progression of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

miR‑29a‑3p inhibits the malignant characteristics of non‑small cell lung cancer cells by reducing the activity of the Wnt/β‑catenin signaling pathway

Zhang

Han

et al. 2022

Oncol Lett

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MicroRNAs (miRNAs) can influence non-small cell lung cancer (NSCLC) in a tumor-suppressive and oncogenic manner. The present study aimed to investigate the effects and underlying mechanisms of miR-29a-3p in NSCLC. NSCLC cell lines (A549, H1299, and H460) and a normal lung epithelial cell line (BEAS-2B) were used. Additionally, a mouse lung tumor xenograft model was established using A549 cells and used to determine the effects of miR-29a-3p on NSCLC in vivo. Tumor volumes were measured every week. The expression of miR-29a-3p in cells and lung tissues were detected by RT-qPCR. Cell proliferation was detected using Cell Counting Kit-8 and EdU assays. Migration and invasion were assessed using wound healing and Transwell invasion assays, respectively. Ki-67 expression was detected using immunohistochemical staining. The expression levels of Wnt3a and β-catenin were determined using western blotting. miR-29a-3p expression was significantly downregulated in NSCLC cells and mice. In contrast to miR-29a-3p knockdown, miR-29a-3p overexpression decreased NSCLC cell proliferation, migration, and invasion as well as tumor growth in in the NSCLC mouse model. Moreover, miR-29a-3p overexpression decreased the protein expression levels of Wnt3a and β-catenin. The inhibitory effects of miR-29a-3p on NSCLC cells were reversed by LiCl (an activator of the Wnt signaling pathway). In conclusion, miR-29a-3p prevented NSCLC tumor growth and cell proliferation, migration, and invasion by inhibiting the Wnt/β-catenin signaling pathway. This finding offers novel insights into the prognosis and treatment of NSCLC.

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MiR-579 Inhibits Lung Adenocarcinoma Cell Proliferation and Metastasis via Binding to CRABP2

Cited by 5 publications

References 25 publications

The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors

The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors

CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α

miR‑29a‑3p inhibits the malignant characteristics of non‑small cell lung cancer cells by reducing the activity of the Wnt/β‑catenin signaling pathway

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