The role of miR-372 in ovarian carcinoma cell proliferation

Guan, Xue; Zong, Zhi‐Hong; Chen, Shuo; Sang, Xiu-Bo; Wu, Dandan; Wang, Lili; Liu, Yao; Zhao, Yang

doi:10.1016/j.gene.2017.04.043

Cited by 19 publications

(17 citation statements)

References 28 publications

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“…Furthermore, low miR-372 expression was correlated with poor prognosis and tumor metastasis in HCC (42). Moreover, the miRNA family was also shown to be a tumor suppressor gene in cervical carcinoma (43), endometrial adenocarcinoma (44) and ovarian carcinoma (45). Nevertheless, the role of the miR-520/ 372/373 family in RCC was largely unknown.…”

Section: Discussionmentioning

confidence: 99%

The E2F1–miR-520/372/373–SPOP Axis Modulates Progression of Renal Carcinoma

Ding

Wang

et al. 2018

Cancer Research

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Although renal cell carcinoma (RCC) is the most malignant urologic cancer, its pathogenesis remains unclear, and effective treatments for advanced RCC are still lacking. Here, we report that a novel E2F1-miR-520/372/373-SPOP axis controls RCC carcinogenesis. Speckle-type POZ protein (SPOP) was upregulated in over 90% of RCC tissues, whereas the miR-520/372/ 373 family was downregulated and correlated inversely with SPOP protein levels in RCC tissues. The miR-520/372/373 family targeted the SPOP 3 0-UTR and suppressed SPOP protein expression, leading to elevation of PTEN and DUSP7 levels and, consequently, decreased proliferation, invasion/ migration, and metastasis of RCC cells in vitro and in vivo. Tail-vein delivery of therapeutic miR-520/372/373 family significantly decreased both tumor size and lung metastasis ratio in mice bearing orthotopic xenograft tumors. Decreased expression of miR-520/372/373 family was mediated by transcription factor E2F1. In conclusion, our results demonstrate that the E2F1-miR-520/372/373-SPOP axis functions as a key signaling pathway in RCC progression and metastasis and represents a promising opportunity for targeted therapies. Significance: These findings show that the E2F1-miR-520/ 372/373 family-SPOP axis promotes RCC progression, thereby contributing to our understanding of RCC pathogenesis and unveiling new avenues for more effective targeted therapies. Cancer Res; 78(24); 6771-84. Ó2018 AACR.

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Section: Discussionmentioning

confidence: 99%

The E2F1–miR-520/372/373–SPOP Axis Modulates Progression of Renal Carcinoma

Ding

Wang

et al. 2018

Cancer Research

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“…The cell cycle regulators cyclin-dependent kinase inhibitor 1A (p21/CDKN1A) and large tumor suppressor kinase 2 (LATS2) are known targets of miR-372 in human ESCs (Qi et al 2009) and in testicular germ cell tumors (Voorhoeve et al 2006). Moreover, they have been further confirmed as miR-372 targets in nasopharyngeal (Tan et al 2014), ovarian (Guan et al 2017) and colorectal (Yamashita et al 2012) cancer cells. Based on these considerations, we tested the hypothesis that CDKN1A and LATS2 could be regulated by miR-372 in parathyroid tumor cells.…”

Section: Mir-372 Targets P21/cdkn1a and Lats2 Genes In Parathyroid Tumentioning

confidence: 99%

The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells

Verdelli¹,

Forno²,

Morotti³

et al. 2018

Endocrine-Related Cancer

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Parathyroid tumors deregulate microRNAs belonging to the two clusters on the chromosome 19, the C19MC and miR-371-373 clusters. Here, we report that the embryonic miR-372 is aberrantly expressed in half of parathyroid adenomas (PAds) in most of atypical adenomas and carcinomas ( = 15). Through hybridization, we identified that miR-372-positive parathyroid tumor cells were scattered throughout the tumor parenchyma. In PAd-derived cells, ectopic miR-372 inhibited the expression of its targets/p21 and LATS2 at both mRNA and protein levels. Although the viability of parathyroid cells was not affected by miR-372 overexpression, the miRNA blunted camptothecin-induced apoptosis in primary PAd-derived cultures. miR-372 overexpression in parathyroid tumor cells increased parathormone () mRNA levels, and it positively correlated with circulating PTH levels. Conversely, the parathyroid-specific genes and were not affected by miR-372 mimic transfection. Finally, miR-372 dampened the Wnt pathway in parathyroid tumor cells through DKK1 upregulation. In conclusion, miR-372 is a novel mechanism exploited by a subset of parathyroid tumor cells to partially decrease sensitivity to apoptosis, to increase PTH synthesis and to deregulate Wnt signaling.

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“…23,24 Once initiated, ATAD2 expression leads to several positive feedback loops, dependent on tissue type, the products of which will further upregulate ATAD2, 16 cell proliferation, and survival genes. ATAD2 overexpression is associated with a myriad of unrelated cancers, including breast, 20,23,[25][26][27][28] colorectal, [29][30][31] endometrial [32][33][34] gastric, 31,35,36 hepatocellular carcinoma, [37][38][39][40] lung, 25,41,42 ovarian, 43,44 and prostate. 16,45,46 Up regulation of ATAD2 is often correlated with poor patient outcomes, and can be used as prognostic marker.…”

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confidence: 99%

Disulfide bridge formation influences ligand recognition by the ATAD2 bromodomain

et al. 2018

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The ATPase family, AAA domain-containing protein 2 (ATAD2) has a C-terminal bromodomain, which functions as a chromatin reader domain recognizing acetylated lysine on the histone tails within the nucleosome. ATAD2 is overexpressed in many cancers and its expression is correlated with poor patient outcomes, making it an attractive therapeutic target and potential biomarker. We solved the crystal structure of the ATAD2 bromodomain and found that it contains a disulfide bridge near the base of the acetyllysine binding pocket (Cys1057-Cys1079). Sitedirected mutagenesis revealed that removal of a free C-terminal cysteine (C1101) residue greatly improved the solubility of the ATAD2 bromodomain in vitro. Isothermal titration calorimetry experiments in combination with the Ellman's assay demonstrated that formation of an intramolecular disulfide bridge negatively impacts the ligand binding affinities and alters the thermodynamic parameters of the ATAD2 bromodomain interaction with a histone H4K5ac peptide as well as a small molecule bromodomain ligand. Molecular dynamics simulations indicate that the formation of the disulfide bridge in the ATAD2 bromodomain does not alter the structure of the folded state or flexibility of the acetyllysine binding pocket. However, consideration of this unique structural feature should be taken into account when examining ligandbinding affinity, or in the design of new bromodomain inhibitor compounds that interact with this acetyllysine reader module. K E Y W O R D S acetyllysine, ATAD2, bromodomain inhibitor, chromatin reader domain, disulfide bridge, epigenetics, histone, post-translational modification

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The role of miR-372 in ovarian carcinoma cell proliferation

Cited by 19 publications

References 28 publications

The E2F1–miR-520/372/373–SPOP Axis Modulates Progression of Renal Carcinoma

The E2F1–miR-520/372/373–SPOP Axis Modulates Progression of Renal Carcinoma

The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells

Disulfide bridge formation influences ligand recognition by the ATAD2 bromodomain

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