Evidence map›Paper›PMID 33645623›Full record

ArticleBioscience reports2021

Inhibition of lncRNA-NEAT1 sensitizes 5-Fu resistant cervical cancer cells through de-repressing the microRNA-34a/LDHA axis.

Xuecheng Shao, Xuehui Zheng, Dan Ma, Yang Liu, Guoyan Liu

Open access · goldAbstract read
In one paragraph

Article in Bioscience reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

35 citing papers in PubMed, 42 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

5 authors at 4 institutions in 1 country.

Xuecheng ShaoDepartment of Obstetrics and Gynecology, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China.
Xuehui ZhengDepartment of Obstetrics and Gynecology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin 300170, China.
Dan MaDepartment of Obstetrics and Gynecology, Tianjin Third Central Hospital, Tianjin 300170, China.
Yang LiuDepartment of Obstetrics and Gynecology, Tianjin Third Central Hospital, Tianjin 300170, China.
Guoyan LiuDepartment of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin 300170, China.ORCID 0000-0002-3637-4296
Tianjin Third Central Hospital · CNChinese People's Armed Police General Hospital · CNTianjin Medical University · CNTianjin Medical University General Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cervical cancer is one of the most diagnosed malignancies among females. The 5-fluorouracil (5-Fu) is a widely used chemotherapeutic agent against diverse cancers. Despite the initially encouraging progresses, a fraction of cervical cancer patients developed 5-Fu resistance. We detected that nuclear-rich transcripts 1 (NEAT1) was significantly up-regulated in cervical cancer tissues and cell lines. Moreover, NEAT1 was positively associated with 5-Fu resistance. Furthermore, expression of NEAT1 was significantly up-regulated in 5-Fu resistant CaSki cervical cancer cells. Knocking down NEAT1 by shRNA dramatically promoted the sensitivity of 5-Fu resistant CaSki cells. We observed a negative correlation between long noncoding RNA (lncRNA)-NEAT1 and miR-34a in cervical cancer patient tissues. Overexpression of miR-34a significantly sensitized 5-Fu resistant cells. Bioinformatics analysis uncovered that NEAT1 functions as a competitive endogenous RNA (ceRNA) of miR-34a in cervical cancer cells via sponging it at multiple sites to suppress expression of miR-34a. This negative association between NEAT1 and miR-34a was further verified in cervical cancer tissues. We found the 5-Fu resistant cells displayed significantly increased glycolysis rate. Overexpression of miR-34a suppressed cellular glycolysis rate and sensitized 5-Fu resistant cells through direct targeting the 3'-untranslated region (UTR) of LDHA, a glycolysis key enzyme. Importantly, knocking down NEAT1 successfully down-regulated LDHA expressions and glycolysis rate of cervical cancer cells by up-regulating miR-34a, a process could be further rescued by miR-34a inhibition. Finally, we demonstrated inhibition of NEAT1 significantly sensitized cervical cancer cells to 5-Fu through the miR-34a/LDHA pathway. In summary, the present study suggests a new molecular mechanism for the NEAT1-mediated 5-Fu resistance via the miR-34a/LDHA-glycolysis axis.

Indexed as

Drug Resistance, NeoplasmAntimetabolites, AntineoplasticFemaleFluorouracilGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticGlycolysisHeLa CellsHumansL-Lactate DehydrogenaseMicroRNAsRNA, Long NoncodingSignal TransductionUterine Cervical NeoplasmsAntimetabolites, AntineoplasticFluorouracilLDHA protein, humanL-Lactate DehydrogenaseMicroRNAsMIRN34 microRNA, humanNEAT1 long non-coding RNA, humanRNA, Long Noncoding5-Fu resistancecervical cancerlncRNA-NEAT1miR–34aWarburg effect

Identifiers

PMID33645623
PMCPMC8298262
OpenAlexW3133755305

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Registered trials

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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.