Evidence map›Paper›PMID 33516270›Full record

ArticleBiomarker research2021

LncRNA APCDD1L-AS1 induces icotinib resistance by inhibition of EGFR autophagic degradation via the miR-1322/miR-1972/miR-324-3p-SIRT5 axis in lung adenocarcinoma.

Jie Wu, Chunlei Zheng, Yizhe Wang, Zichang Yang, Ce Li, Wanxia Fang, Yue Jin, Kezuo Hou, Yang Cheng, Jianfei Qi and 4 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomarker research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.6field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Jie Wu *Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, No.155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China.
Chunlei Zheng *Department of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Yizhe WangDepartment of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, No.155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China.
Zichang YangDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Ce LiDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Wanxia FangDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Yue JinDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Kezuo HouDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Yang ChengDepartment of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, No.155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China.
Jianfei QiMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA.
Xiujuan QuDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Yunpeng LiuDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China.
Xiaofang CheDepartment of Medical Oncology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, China. xfche@cmu.edu.cn.
Xuejun HuDepartment of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, No.155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China. xjhu@cmu.edu.cn.
China Medical University · CNFirst Hospital of China Medical University · CNUniversity of Maryland, Baltimore · US

Funding

National Natural Science Foundation of China 8147219National Natural Science Foundation of China 81972197Science and Technology Plan Project of Liaoning Province 2019-ZD-0777Science and Technology Plan Project of Shenyang City 19-112-4-099The Key Research and Development Program of Liaoning Province 2018225060
6 · The paper itself

Abstract

backgroundEpidermal growth factor receptor-tyrosinase kinase inhibitor (EGFR-TKI) resistance is the major obstacle in the treatment of lung adenocarcinoma (LUAD) patients harboring EGFR-sensitive mutations. However, the long non-coding RNAs (lncRNAs) related to EGFR-TKIs resistance and their functional mechanisms are still largely unknown. This study aimed to investigate the role and regulatory mechanism of lncRNA APCDD1L-AS1 in icotinib resistance of lung cancer.

methodsMolecular approaches including qRT-PCR, MTT assay, colony formation, RNA interference and cell transfection, RNA immunoprecipitation (RIP), dual luciferase reporter assay, RNA fluorescence in situ hybridization, TUNEL assay, flow cytometry, immunoblotting, xenograft model and transcriptome sequencing were used to investigate the mechanism of APCDD1L-AS1 in icotinib resistance.

resultsA novel lncRNA, APCDD1L-AS1 was identified as the most significantly upregulated lncRNA in icotinib-resistant LUAD cells by the transcriptome sequencing and differential lncRNA expression analysis. We found that APCDD1L-AS1 not only promoted icotinib resistance, but also upregulated the protein expression level of EGFR. Mechanistically, APCDD1L-AS1 promoted icotinib resistance and EGFR upregulation by sponging with miR-1322/miR-1972/miR-324-3p to remove the transcription inhibition of SIRT5. Furthermore, SIRT5 elevated EGFR expression and activation by inhibiting the autophagic degradation of EGFR, finally promoting icotinib resistance. Consistently, the autophagy initiator rapamycin could decrease EGFR levels and increase the sensitivity of icotinib-resistant LUAD cells to icotinib.

conclusionAPCDD1L-AS1 could promote icotinib resistance by inhibiting autophagic degradation of EGFR via the miR-1322/miR-1972/miR-324-3p-SIRT5 axis. The combination of autophagy initiator and EGFR-TKIs might serve as a potential new strategy for overcoming EGFR-TKIs resistance in LUAD patients.

Indexed as

AutophagyIcotinib-resistanceLncRNA APCDD1L-AS1Lung adenocarcinomaSIRT5

Identifiers

PMID33516270
PMCPMC7847171
OpenAlexW3128712947

What Socratic 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 Socratic graph.