LINC00885 promotes cervical cancer progression through sponging miR-3150b-3p and upregulating BAZ2A

Background Cervical cancer (CC) is one of the most common malignancies affecting female worldwide. Long non-coding RNAs (lncRNAs) are increasingly indicated as crucial participants and promising therapeutic targets in human cancers. The main objective of this study was to explore the functions and mechanism of LINC00885 in CC. Methods RT-qPCR and western blot were used to detect RNA and protein levels. Functional and mechanism assays were respectively done for the analysis of cell behaviors and molecular interplays. Results Long intergenic non-coding RNA 885 (LINC00885) was discovered to be upregulated in CC tissues and cell lines through bioinformatics analysis and RT-qPCR. Overexpression of LINC00885 promoted proliferation and inhibited apoptosis, whereas its silence exerted opposite effects. The cytoplasmic localization of LINC00885 was ascertained and furthermore, LINC00885 competitively bound with miR-3150b-3p to upregulate BAZ2A expression in CC cells. Rescue assays confirmed that LINC00885 regulated CC proliferation and apoptosis through miR-3150b-3p/BAZ2A axis. Finally, we confirmed that LINC00885 aggravated tumor growth through animal experiments. Conclusions LINC00885 exerted oncogenic function in CC via regulating miR-3150b-3p/BAZ2A axis. These findings suggested LINC00885 might serve as a potential promising therapeutic target for CC patients.

H3K27ac-activated EGFR-AS1 promotes cell growth in cervical cancer through ACTN4-mediated WNT pathway

Background Recently, extensive studies unveiled that lncRNAs exert critical function in the development and progression of cervical cancer (CC). EGFR-AS1 is a novel lncRNA which has not been well-explored in CC. Aims Our study aimed to research the function and molecular mechanism of EGFR-AS1 in CC cells. qRT-PCR analysis was performed to detect gene expression. Colony formation, EdU, flow cytometry, TUNEL, western blot and transwell assays were performed to assess the effect of EGFR-AS1 on CC cell growth. The regulatory mechanism of EGFR-AS1 was dug out through mechanism experiments. Results EGFR-AS1 was notably overexpressed in CC cell lines. Loss-of-functional experiments revealed that EGFR-AS1 promoted CC cell proliferation, migration and invasion, and suppressed cell apoptosis. Mechanistically, up-regulation of EGFR-AS1 was attributed to the activation of H3K27 acetylation (H3K27ac). Further, EGFR-AS1 was revealed to function as miR-2355-5p sponge. Additionally, miR-2355-5p was down-regulated in CC cells and ACTN4 was identified as a target gene of miR-2355-5p. Ultimately, overexpressed ACTN4 could reserve the suppressive role of EGFR-AS1 silencing in CC cell growth. Last but not least, EGFR-AS1 facilitated CC cell growth via ACTN4-mediated WNT pathway. Conclusions H3K27ac-activated EGFR-AS1 sponged miR-2355-5p and promoted CC cell growth through ACTN4-mediated WNT pathway.

LncRNA MIR205HG accelerates cell proliferation, migration and invasion in hepatoblastoma through the activation of MAPK signaling pathway and PI3K/AKT signaling pathway

Background Hepatoblastoma (HB) is identified to be the most common liver malignancy which occurs in children. Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes and diseases, including HB. LncRNA MIR205 host gene (MIR205HG) has been investigated in multiple cancers, however, its role in HB remains to be elucidated. Methods MIR205HG expression was analyzed by RT-qPCR. EdU, colony formation and transwell assays were implemented to measure the biological function of MIR205HG on the progression of HB. Mechanism assays were carried out to probe into the underlying mechanism of MIR205HG in HB cells. Results MIR205HG was significantly overexpressed in HB. Moreover, MIR205HG inhibition suppressed the proliferative, migratory and invasive capacities of HB cells. Furthermore, MIR205HG competitively bound to microRNA-514a-5p (miR-514a-5p) and targeted mitogen-activated protein kinase 9 (MAPK9) to stimulate mitogen activated protein kinase (MAPK) signaling pathway. Besides, MIR205HG also served as a sponge for microRNA-205-5p (miR-205-5p) to activate the PI3K/AKT signaling pathway. Conclusion MIR205HG drives the progression of HB which might provide an efficient marker and new therapeutic target for HB.

LncRNA NORAD facilitates oral squamous cell carcinoma progression by sponging miR-577 to enhance TPM4

Background Long non-coding RNAs (lncRNAs) have been reported to be vital factors to affect the expression of genes and proteins. Also, it has been proved that the abnormal expression or mutation of lncRNAs stands as a signal of metastasis and proliferation of cancer. Nevertheless, the majority of lncRNAs still need to be explored in abundant cancers especially in oral squamous cell carcinoma (OSCC). Methods RT-qPCR assays were applied to test the expression of RNAs. Mechanism assays were performed to verify the combination among NORAD, TPM4 and miR-577. Also, functional assays were conducted to verify the function of RNAs on OSCC cells. Results LncRNA NORAD was highly expressed in OSCC tissues and cells. NORAD silencing repressed the biological behaviors of OSCC cells. MiR-577 was found in OSCC with low expression, and RIP assays illustrated that NORAD, miR-577 and TPM4 coexisted in RNA-induced silencing complexes. Rescue assays proved that the overexpression of TPM4 could recover the effect of NORAD silencing on OSCC progression. Conclusions It was revealed that NORAD functioned as a tumor promoter to sponge miR-577 thus elevating TPM4 in OSCC, which indicated that NORAD was worthy to be studied as a target for the treatment of OSCC.

HIV-1LAI Nef blocks the development of hematopoietic stem/progenitor cells into myeloid-erythroid lineage cells

Background A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection. Results In the current study we investigated the influence of HIV-1LAI Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs. Conclusions Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities.

Integrative analysis of the salt stress response in cyanobacteria

Microorganisms evolved specific acclimation strategies to thrive in environments of high or fluctuating salinities. Here, salt acclimation in the model cyanobacterium Synechocystis sp. PCC 6803 was analyzed by integrating transcriptomic, proteomic and metabolomic data. A dynamic reorganization of the transcriptome occurred during the first hours after salt shock, e.g. involving the upregulation of genes to activate compatible solute biochemistry balancing osmotic pressure. The massive accumulation of glucosylglycerol then had a measurable impact on the overall carbon and nitrogen metabolism. In addition, we observed the coordinated induction of putative regulatory RNAs and of several proteins known for their involvement in other stress responses. Overall, salt-induced changes in the proteome and transcriptome showed good correlations, especially among the stably up-regulated proteins and their transcripts. We define an extended salt stimulon comprising proteins directly or indirectly related to compatible solute metabolism, ion and water movements, and a distinct set of regulatory RNAs involved in post-transcriptional regulation. Our comprehensive data set provides the basis for engineering cyanobacterial salt tolerance and to further understand its regulation.

Study on the mechanism of LOXL1-AS1/miR-3614-5p/YY1 signal axis in the malignant phenotype regulation of hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality worldwide. Accumulating researches have indicated that long non‑coding RNAs (lncRNAs) are involved in varies human cancers, including HCC. Nevertheless, the specific molecular mechanism of lncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in HCC is still unclear. Methods LOXL1-AS1 expression was tested via qRT-PCR in HCC cells. Functional and mechanism assays were respectively done to evaluate the biological functions of HCC cells and the potential interaction of LOXL1-AS1 and other factors. Results We discovered that LOXL1-AS1 was high expressed in HCC cells. Inhibition of LOXL1-AS1 repressed cell proliferation, migration and invasion, but enhanced cell apoptosis in HCC. Further, miR-3614-5p was proven to be sponged by LOXL1-AS1. Additionally, Yin Yang 1 (YY1) was proven as the target gene of miR-3614-5p, and YY1 depletion could repress HCC cell malignant behaviors. YY1 could also transcriptionally activate LOXL1-AS1 expression. In rescue assays, we confirmed that overexpression of YY1 or miR-3614-5p inhibition could reverse the suppressive effects of LOXL1-AS1 silence on the malignant behaviors of HCC cells. Conclusion In short, LOXL1-AS1/miR-3614-5p/YY1 forms a positive loop in modulating HCC cell malignant behaviors.

A link between mitotic defects and mitotic catastrophe: detection and cell fate

Although the phenomenon of mitotic catastrophe was first described more than 80 years ago, only recently has this term been used to explain a mechanism of cell death linked to delayed mitosis. Several mechanisms have been suggested for mitotic catastrophe development and cell fate. Depending on molecular perturbations, mitotic catastrophe can end in three types of cell death, namely apoptosis, necrosis, or autophagy. Moreover, mitotic catastrophe can be associated with different types of cell aging, the development of which negatively affects tumor elimination and, consequently, reduces the therapeutic effect. The effective triggering of mitotic catastrophe in clinical practice requires induction of DNA damage as well as inhibition of the molecular pathways that regulate cell cycle arrest and DNA repair. Here we discuss various methods to detect mitotic catastrophe, the mechanisms of its development, and the attempts to use this phenomenon in cancer treatment.

Rab32 uses its effector reticulon 3L to trigger autophagic degradation of mitochondria-associated membrane (MAM) proteins

Background Rab32 is a small GTPase associated with multiple organelles but is particularly enriched at the endoplasmic reticulum (ER). Here, it controls targeting to mitochondria-ER contacts (MERCs), thus influencing composition of the mitochondria-associated membrane (MAM). Moreover, Rab32 regulates mitochondrial membrane dynamics via its effector dynamin-related protein 1 (Drp1). Rab32 has also been reported to induce autophagy, an essential pathway targeting intracellular components for their degradation. However, no autophagy-specific effectors have been identified for Rab32. Similarly, the identity of the intracellular membrane targeted by this small GTPase and the type of autophagy it induces are not known yet. Results To investigate the target of autophagic degradation mediated by Rab32, we tested a large panel of organellar proteins. We found that a subset of MERC proteins, including the thioredoxin-related transmembrane protein TMX1, are specifically targeted for degradation in a Rab32-dependent manner. We also identified the long isoform of reticulon-3 (RTN3L), a known ER-phagy receptor, as a Rab32 effector. Conclusions Rab32 promotes degradation of mitochondrial-proximal ER membranes through autophagy with the help of RTN3L. We propose to call this type of selective autophagy “MAM-phagy”.

Principles and biological concepts of heredity before Mendel

The knowledge of the history of a subject stimulates understanding. As we study how other people have made scientific breakthroughs, we develop the breadth of imagination that would inspire us to make new discoveries of our own. This perspective certainly applies to the teaching of genetics as hallmarked by the pea experiments of Mendel. Common questions students have in reading Mendel’s paper for the first time is how it compares to other botanical, agricultural, and biological texts from the early and mid-nineteenth centuries; and, more precisely, how Mendel’s approach to, and terminology for debating, topics of heredity compare to those of his contemporaries? Unfortunately, textbooks are often unavailing in answering such questions. It is very common to find an introduction about heredity in genetic textbooks covering Mendel without mentions of preceding breeding experiments carried out in his alma mater. This does not help students to understand how Mendel came to ask the questions he did, why he did, or why he planned his pea studies the way he did. Furthermore, the standard textbook “sketch” of genetics does not allow students to consider how discoveries could have been framed and inspired so differently in various parts of the world within a single historical time. In our review we provide an extended overview bridging this gap by showing how different streams of ideas lead to the eventual foundation of particulate inheritance as a scientific discipline. We close our narrative with investigations on the origins of animal and plant breeding in Central Europe prior to Mendel in Kőszeg and Brno, where vigorous debates touched on basic issues of heredity from the early eighteenth-century eventually reaching a pinnacle coining the basic questions: What is inherited and how is it passed on from one generation to another?