Evidence map›Paper›PMID 30987652›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

Restoration of mutant K-Ras repressed miR-199b inhibits K-Ras mutant non-small cell lung cancer progression.

Hua Jin, Yoonjeong Jang, Nian Cheng, Qing Li, Peng-Fei Cui, Zhi-Wei Zhou, Hu-Lin Jiang, Myung-Haing Cho, Kenneth D Westover, Qun-You Tan and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

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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

11 authors.

Hua JinDepartment of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, China.
Yoonjeong JangLaboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea.
Nian ChengDepartment of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, China.
Qing LiCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, China.
Peng-Fei CuiState Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
Zhi-Wei ZhouDepartment of Biochemistry and Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Hu-Lin JiangState Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
Myung-Haing ChoLaboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea.
Kenneth D WestoverDepartment of Biochemistry and Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Qun-You TanDepartment of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, China.
Cheng-Xiong XuCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, China. xuchengxiong@hanmail.net.

Funding

National Natural Science Foundation of China 81672283
6 · The paper itself

Abstract

backgroundmiRNAs play crucial role in the progression of K-Ras-mutated nonsmall cell lung cancer (NSCLC). However, most studies have focused on miRNAs that target K-Ras. Here, we investigated miRNAs regulated by mutant K-Ras and their functions.

methodsmiRNAs regulated by mutant K-Ras were screened using miRNA arrays. miR-199b expression levels were measured by qRT-PCR. The protein expression levels were measured using Western blot and immunohistochemistry. The effects of miR-199b on NSCLC were examined both in vitro and in vivo by overexpressing or inhibiting miR-199b. DNA methylation was measured by bisulfite sequencing.

resultsAn inverse correlation was observed between K-Ras mutation status and miR-199b levels in NSCLC specimens and cell lines. The inhibition of miR-199b stimulated NSCLC growth and metastasis, while restoration of miR-199b suppressed K-Ras mutation-driven lung tumorigenesis as well as K-Ras-mutated NSCLC growth and metastasis. miR-199b inactivated ERK and Akt pathways by targeting K-Ras, KSR2, PIK3R1, Akt1, and Rheb1. Furthermore, we determined that mutant K-Ras inhibits miR-199b expression by increasing miR-199b promoter methylation.

conclusionOur findings suggest that mutant K-Ras plays an oncogenic role through downregulating miR-199b in NSCLC and that overexpression of miR-199b is a novel strategy for the treatment of K-Ras-mutated NSCLC.

Indexed as

Carcinoma, Non-Small-Cell LungCell Line, TumorCell MovementCell ProliferationCell Transformation, NeoplasticDisease ProgressionDNA MethylationExtracellular Signal-Regulated MAP KinasesGene Expression Regulation, NeoplasticGenes, ReporterHumansLung NeoplasmsMicroRNAsModels, MolecularMutationProto-Oncogene Proteins c-aktExtracellular Signal-Regulated MAP KinasesKRAS protein, humanMicroRNAsmirn199 microRNA, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)K-RasmiR-199bNon-small cell lung cancer

Identifiers

PMID30987652
PMCPMC6466664

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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.