Journal of Genetics and Genomics

miR-503-3p promotes epithelial–mesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin

Zitong Zhao, Xinyi Fan, Lanfang Jiang, Zhongqiu Xu, Liyan Xue, Qimin Zhan, Yongmei Song

2017, 44(2): 75-84. doi: 10.1016/j.jgg.2016.10.005

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Abstract:
Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of miR-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined. Here, we found that miR-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified miR-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of miR-503-3p in breast cancer cells inhibited expression of epithelial–mesenchymal transition (EMT)-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their mRNA 3′ untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for miR-503-3p in induction of breast cancer EMT and suggest that plasma miR-503-3p may be a useful diagnostic biomarker for breast cancer.

ISWI ATP-dependent remodeling of nucleoplasmic ω-speckles in the brain of Drosophila melanogaster

Luca Lo Piccolo, Andrea Attardi, Rosa Bonaccorso, Lorenzo Li Greci, Giorgio Giurato, Antonia Maria Rita Ingrassia, Maria Cristina Onorati

2017, 44(2): 85-94. doi: 10.1016/j.jgg.2016.12.002

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Abstract:
Heterogeneous nuclear ribonucleoproteins (hnRNPs) belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs. These proteins participate in every step of mRNA cycle, such as mRNA export, localization, translation, stability and alternative splicing. At least 14 major hnRNPs, which have structural and functional homologues in mammals, are expressed inDrosophila melanogaster. Until now, six of these hnRNPs are known to be nucleus-localized and associated with the long non-coding RNA (lncRNA) heat shock responsive ω (hsrω) in the omega speckle compartments (ω-speckles). The chromatin remodeler ISWI is the catalytic subunit of several ATP-dependent chromatin-remodeling complexes, and it is an essential factor for organization of ω-speckles. Indeed, in ISWI null mutant, severe defects in ω-speckles structure are detectable. Here, we clarify the role of ISWI in the hnRNPs‒hsrω interaction. Moreover, we describe how ISWI by its remodeling activity, controls hsrω and hnRNPs engagement in ω-speckles. Finally, we demonstrate that the sequestration of hnRNPs in ω-speckles nuclear compartment is a fundamental event in gene expression control and represents a key step in the regulation of several pathways.

Regulators of alternative polyadenylation operate at the transition from mitosis to meiosis

Lingjuan Shan, Chan Wu, Di Chen, Lei Hou, Xin Li, Lixia Wang, Xiao Chu, Yifeng Hou, Zhaohui Wang

2017, 44(2): 95-106. doi: 10.1016/j.jgg.2016.12.007

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Abstract:
In the sexually reproductive organisms, gametes are produced by meiosis following a limited mitotic amplification. However, the intrinsic program switching cells from mitotic to meiotic cycle is unclear. Alternative polyadenylation (APA) is a highly conserved means of gene regulation and is achieved by the RNA 3′-processing machinery to generate diverse 3′UTR profiles. In Drosophila spermatogenesis, we observed distinct profiles of transcriptome-wide 3′UTR between mitotic and meiotic cells. In mutant germ cells stuck in mitosis, 3′UTRs of hundreds of genes were consistently shifted. Remarkably, altering the levels of multiple 3′-processing factors disrupted germline's progression to meiosis, indicative of APA's active role in this transition. An RNA-binding protein (RBP) Tut could directly bind 3′UTRs of 3′-processing factors whose expressions were repressed in the presence of Tut-containing complex. Further, we demonstrated that this RBP complex could execute the repression post-transcriptionally by recruiting CCR4/Twin of deadenylation complex. Thus, we propose that an RBP complex regulates the dynamic APA profile to promote the mitosis-to-meiosis transition.

LMM5.1 and LMM5.4, two eukaryotic translation elongation factor 1A-like gene family members, negatively affect cell death and disease resistance in rice

Jiying Zhao, Pengcheng Liu, Chunrong Li, Yanyan Wang, Lequn Guo, Guanghuai Jiang, Wenxue Zhai

2017, 44(2): 107-118. doi: 10.1016/j.jgg.2016.12.005

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Abstract:
Lesion mimic mutant (LMM) genes, stimulating lesion formation in the absence of pathogens, play significant roles in immune response. In this study, we characterized a rice lesion mimic mutant, lmm5, which displayed light-dependent spontaneous lesions. Additionally, lmm5 plants exhibited enhanced resistance to all of the tested races of Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae (Xoo) by increasing the expression of defense-related genes and the accumulation of hydrogen peroxide. Genetic analysis showed that the lesion mimic phenotype of lmm5 was controlled by two genes, lmm5.1 and lmm5.4, which were isolated with a map-based cloning strategy. Remarkably, LMM5.1 and LMM5.4 share a 97.4% amino acid sequence identity, and they each encode a eukaryotic translation elongation factor 1A (eEF1A)-like protein. Besides, LMM5.1 and LMM5.4 were expressed in a tissue-specific and an indica-specific manner, respectively. In addition, high-throughput mRNA sequencing analysis confirmed that the basal immunity was constitutively activated in the lmm5 mutant. Taken together, these results suggest that the homologous eEF1A-like genes, LMM5.1 and LMM5.4, negatively affect cell death and disease resistance in rice.

ONGene: A literature-based database for human oncogenes

Yining Liu, Jingchun Sun, Min Zhao

2017, 44(2): 119-121. doi: 10.1016/j.jgg.2016.12.004

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Abstract:

Neuronal insulin receptor mediates a positive feedback regulation of insulin biosynthesis in Drosophila

Jie Ye, Danping Chen, Yue Yu, Liming Wang

2017, 44(2): 123-125. doi: 10.1016/j.jgg.2016.12.006

Abstract (99) HTML PDF (2)

Abstract:

2017 Vol. 44, No. 2