Evidence map›Paper›PMID 34356326›Full record

ArticleAntioxidants (Basel, Switzerland)2021

A Novel mRNA-Mediated and MicroRNA-Guided Approach to Specifically Eradicate Drug-Resistant Hepatocellular Carcinoma Cell Lines by Se-Methylselenocysteine.

Arun Kumar Selvam, Rim Jawad, Roberto Gramignoli, Adnane Achour, Hugh Salter, Mikael Björnstedt

Open access · goldAbstract read
In one paragraph

Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 22% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy.International journal of molecular sciences · 2022
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. International journal of molecular sciences · 2023
    Article
  9. Article
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

6 authors at 1 institution in 2 countries.

Arun Kumar SelvamDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.ORCID 0000-0002-9854-2048
Rim JawadDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
Roberto GramignoliDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.ORCID 0000-0003-3362-4170
Adnane AchourScience for Life Laboratory, Department of Medicine Solna, Karolinska Institute, & Division of Infectious Diseases, Karolinska University Hospital, SE-171 77 Solna, Sweden.ORCID 0000-0003-0432-710X
Hugh SalterDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
Mikael BjörnstedtDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.ORCID 0000-0003-2831-3837
Karolinska University Hospital · SE

Funding

Cancerfonden 180429Insamlingsstiftelsen Cancer- och Allergifonden 206Radiumhemmets Forskningsfonder 171023
6 · The paper itself

Abstract

Despite progress in the treatment of non-visceral malignancies, the prognosis remains poor for malignancies of visceral organs and novel therapeutic approaches are urgently required. We evaluated a novel therapeutic regimen based on treatment with Se-methylselenocysteine (MSC) and concomitant tumor-specific induction of Kynurenine aminotransferase 1 (KYAT1) in hepatocellular carcinoma (HCC) cell lines, using either vector-based and/or lipid nanoparticle-mediated delivery of mRNA. Supplementation of MSC in KYAT1 overexpressed cells resulted in significantly increased cytotoxicity, due to ROS formation, as compared to MSC alone. Furthermore, microRNA antisense-targeted sites for miR122, known to be widely expressed in normal hepatocytes while downregulated in hepatocellular carcinoma, were added to specifically limit cytotoxicity in HCC cells, thereby limiting the off-target effects. KYAT1 expression was significantly reduced in cells with high levels of miR122 supporting the concept of miR-guided induction of tumor-specific cytotoxicity. The addition of alpha-ketoacid favored the production of methylselenol, enhancing the cytotoxic efficacy of MSC in HCC cells, with no effects on primary human hepatocytes. Altogether, the proposed regimen offers great potential to safely and specifically target hepatic tumors that are currently untreatable.

Indexed as

alpha-keto acidhepatocellular carcinomakynurenine aminotransferases 1lipid nanoparticlemiRNASe-methylselenocysteine

Identifiers

PMID34356326
PMCPMC8301172
OpenAlexW3182325929

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.