Evidence map›Paper›PMID 25743594›Full record

ArticleMolecular cancer2015

Inhibition of nucleoporin member Nup214 expression by miR-133b perturbs mitotic timing and leads to cell death.

Sumana Bhattacharjya, Kumar Singha Roy, Abira Ganguly, Shreya Sarkar, Chinmay K Panda, Dibyendu Bhattacharyya, Nitai P Bhattacharyya, Susanta Roychoudhury

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Sumana BhattacharjyaCancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4, Raja S.C. Mullick Road, Kolkata, 700 032, India. sumana.rb@gmail.com.
Kumar Singha RoyCancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4, Raja S.C. Mullick Road, Kolkata, 700 032, India. kumarsingharoy88@gmail.com.
Abira GangulyTata Memorial Centre, ACTREC Sector 22, Navi Mumbai, Kharghar, 410210, India. asgc.ganguly@gmail.com.
Shreya SarkarDepartment of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, India. shreya.sarkar.momo@gmail.com.
Chinmay K PandaDepartment of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, India. ckpanda.cnci@gmail.com.
Dibyendu BhattacharyyaTata Memorial Centre, ACTREC Sector 22, Navi Mumbai, Kharghar, 410210, India. dbhattacharyya@actrec.gov.in.
Nitai P BhattacharyyaCrystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata, 700 064, India. nitai.bhattacharyya@gmail.com.
Susanta RoychoudhuryCancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4, Raja S.C. Mullick Road, Kolkata, 700 032, India. susantarc@gmail.com.
Chittaranjan National Cancer Institute · INIndian Institute of Chemical Biology · INTata Memorial Hospital · INCouncil of Scientific and Industrial Research · INSaha Institute of Nuclear Physics · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNucleoporins mediate nucleocytoplasmic exchange of macromolecules and several have been assigned active mitotic functions. Nucleoporins can participate in various mitotic functions like spindle assembly, kinetochore organisation and chromosome segregation- important for genome integrity. Pathways to genome integrity are frequently deregulated in cancer and many are regulated in part by microRNAs. Indeed, altered levels of numerous microRNAs have frequently been associated with tumorigenesis. Here, we unveil a microRNA-mediated regulation of the nucleoporin Nup214 and its downstream effect on genome integrity.

methodsDatabases/bioinformatic tools such as miRBase, Oncomine and RNAhybrid predicted Nup214 as a miR-133b target. To validate this, we used luciferase reporter assays, Real-Time PCR and immuno-blotting. Flow cytometry and immuno-blots of mitotic markers were used to analyse cell cycle pattern upon thymidine synchronization and miR-133b treatment. Mitotic indices and chromosomal abnormalities were assessed by immuno-fluorescence for FITC-tagged phospho-H3 as well as video-microscopy for GFP-tagged histone H4. Annexin V/propidium iodide staining, caspase3/PARP cleavage and colony formation assays were done to investigate cell death upon either miR-133b transfection or NUP214 knockdown by siRNA. UPCI:SCC084, HCT116, HeLa-H4-pEGFP and HEK293 (human oral squamous cell carcinoma, colorectal, cervical carcinomas and embryonic kidney cell lines, respectively) were used. miR-133b and NUP214 expressions were validated in cancer cell lines and tissues by Real-Time PCR.

resultsExamination of head and neck tumour tissues and cancer cell lines revealed that Nup214 and miR-133b expressions are negatively correlated. In vitro, Nup214 was significantly downregulated by ectopic miR-133b. This downregulation elevated mitotic indices and delayed degradation of mitotic marker proteins cyclinB1 and cyclinA and dephosphorylation of H3. Moreover, this mitotic delay enhanced chromosomal abnormalities and apoptosis.

conclusionsWe have identified NUP214, a member of the massive nuclear pore complex, as a novel miR-133b target. Thus, we have shown a hitherto unknown microRNA regulation of mitosis mediated by a member of the nucleoporin family. Based on observations, we also raise some hypotheses regarding transport-dependent/independent functions of Nup214 in this study. Our results hence attempt to explain why miR-133b is generally downregulated in tumours and lay out the potential for Nup214 as a therapeutic target in the treatment of cancer.

Indexed as

ApoptosisCell CycleCell DeathCell LineCell Line, TumorCyclin ACyclin B1Down-RegulationGene Expression Regulation, NeoplasticHCT116 CellsHead and Neck NeoplasmsHEK293 CellsHumansMicroRNAsMitosisNuclear Pore Complex ProteinsCCNB1 protein, humanCyclin ACyclin B1MicroRNAsMIRN133 microRNA, humanNuclear Pore Complex ProteinsNUP214 protein, human

Identifiers

PMID25743594
PMCPMC4335456
OpenAlexW2119871850

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.