Evidence map›Paper›PMID 41813657›Full record

ArticleCell death & disease2026

Declined RTN3 stabilizes DHCR7 to induce cholesterol-dependent tumor progression and MEK inhibitors insensitivity in thyroid cancer.

Anwen Ren, Nan Feng, Tinglin Yang, Zimei Tang, Huan Liu, Yi Li, Qingyi Hu, Zihan Xi, Jiaqing Zhu, Jun Zhou and 4 more

Abstract read
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Anwen Ren *Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0002-9244-3559
Nan Feng *Department of Head-Neck and Thyroid Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Tinglin Yang *Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0009-0008-2504-4591
Zimei TangDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huan LiuDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yi LiDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qingyi HuDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zihan XiDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jiaqing ZhuFirst Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jun ZhouDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jie MingDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nan LiuDepartment of Thyroid Surgery, Qilu Hospital of Shandong University, Jinan, China.
Tao HuangDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. huangtaowh@163.com.ORCID http://orcid.org/0000-0003-2130-8621
Ming XuDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. mingxuwhuh@hust.edu.cn.ORCID http://orcid.org/0000-0002-4388-0701

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82270830National Natural Science Foundation of China (National Science Foundation of China) 82303518National Natural Science Foundation of China (National Science Foundation of China) 82403712National Natural Science Foundation of China (National Science Foundation of China) 82404027National Natural Science Foundation of China (National Science Foundation of China) 82503810National Natural Science Foundation of China (National Science Foundation of China) 82573420Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation) 2022CFB072Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation) ZR2022MH156
6 · The paper itself

Abstract

Mechanism underlying thyroid cancer progression and treatment resistance remains an unsolved problem in clinical practice. Endoplasmic reticulum (ER) proteins modulate cell biosynthesis and mediate tumor progression, among which Reticulon 3 (RTN3) is verified to play important roles in cancers. However, its effect in thyroid cancer has not been clarified. Meanwhile, cholesterol is found to contribute to proliferation and drug resistance in many tumors. As ER is the primary site of cholesterol synthesis, we aimed to study how RTN3 regulates cholesterol concentration and influences tumor progression and sensitivity to MEK inhibitors in thyroid cancer. This study found that RTN3 is low-expressed in thyroid cancer, and is related to poor prognosis and insensitivity to MEK inhibitors. It binds to a cholesterol synthesis enzyme DHCR7 and promotes its ubiquitination. Downregulation of RTN3 lead to stabilization of DHCR7 and elevate cholesterol concentration, activating EGFR/ERK pathway and contributes to progression of thyroid cancer, which can be rescued by HMG-CoA reductase inhibitor Simvastatin. We identified RTN3 as a tumor suppressor and a biomarker of sensitivity to MEK inhibitors and verified the role of cholesterol in drug resistance. The combination of statins provides a novel therapeutic method in patients resistant to MEK inhibitors.

Indexed as

CholesterolDrug Resistance, NeoplasmMembrane ProteinsNerve Tissue ProteinsOxidoreductases Acting on CH-CH Group DonorsProtein Kinase InhibitorsThyroid NeoplasmsAnimalsCarrier ProteinsCell Line, TumorDisease ProgressionFemaleHumansMiceMice, Nude7-dehydrocholesterol reductaseCarrier ProteinsCholesterolMembrane ProteinsNerve Tissue ProteinsOxidoreductases Acting on CH-CH Group DonorsProtein Kinase InhibitorsRTN3 protein, human

Identifiers

PMID41813657
PMCPMC13039173

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.