Evidence map›Paper›PMID 40640851›Full record

ArticleJournal of translational medicine2025

Knocking down hypoxia-induced Semaphorin 6B may attenuate the progression of cervical cancer through regulating macrophage M2 polarization.

Shuyan Yi, Sha Hu, Wenhan Li, Jing Cai, Liqiong Cai, Lufang Wang

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. 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

6 authors.

Shuyan Yi *Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, P.R. China.
Sha Hu *Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, P.R. China.
Wenhan LiDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, P.R. China.
Jing CaiDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, P.R. China.
Liqiong CaiDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, P.R. China. tjcailq@hust.edu.cn.
Lufang WangDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, P.R. China. 2018xh0110@hust.edu.cn.ORCID 0000-0002-6670-0021

Funding

Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education 2024MZFS010Knowledge Innovation Program of Wuhan-Shuguang Project 2023020201020563the Open Research Fund of Hubei Province Key Laboratory of Precision Radiation Oncology 2024ZLJZFL003
6 · The paper itself

Abstract

backgroundCervical cancer is one of the most common malignancies in women, and its progression is closely associated with hypoxia and tumor-associated macrophages (TAMs) polarization in the tumor microenvironment (TME). The dynamic interaction between cancer cells and TAMs in the hypoxic tumor microenvironment is the key to promoting tumor progression. However, the mechanisms underlying this interaction remain unclear.

methodsMacrophages were exposed to hypoxia, and next-generation sequencing was performed to analyze differentially expressed genes. TCGA data were used to identify the up-regulated genes that were independently associated with patient survival. Multiplex immunofluorescence was employed to identify semaphorin 6B (SEMA6B)-positive TAMs in human cervical cancers, and the correlation between their infiltration and clinicopathological characteristics were analyzed. TCGA, GEO, and TIMER databases were used to assess correlations between SEMA6B expression and patient survival and immune cell infiltration patterns. The SEMA6B expression in macrophages was knocked down by using siRNAs. Cell proliferation and mobility were evaluated in vitro, and flow cytometry, PCR and Western Blotting were conducted to determine the polarization of macrophages.

resultsAfter exposure to hypoxia, 236 genes were up-regulated in macrophages. Among them, SEMA6B exhibited a significant association with poor survival. In addition, abundant CD206 + SEMA6B + TAMs were associated with poor prognosis in cervical cancer patients. Database analysis revealed that SEMA6B expression was positively correlated with the infiltration of M2 macrophages and Tregs and negatively correlated with the infiltration of CD4 + and CD8 + T cells. In vitro, knocking down SEMA6B in macrophages inhibited macrophage M2 polarization and the migration ability of macrophages. Furthermore, after coculture of macrophages with SEMA6B knockdown and cervical cancer cells, the proliferation, migration and invasion of SiHa and HeLa cells was significantly reduced in vitro.

conclusionsKnocking down SEMA6B may attenuate the progression of cervical cancer through regulating macrophage M2 polarization. The mechanism of action of SEMA6B on the progression of cervical cancer in vivo still needs further research. Targeting SEMA6B may be a potential immunotherapy approach for treating cervical cancer.

Indexed as

Gene Expression Regulation, NeoplasticMacrophage ActivationSemaphorinsTumor-Associated MacrophagesUterine Cervical NeoplasmsAdultAnimalsCell MovementCell ProliferationCervix UteriDisease ProgressionFemaleGene Knockdown TechniquesHeLa CellsHumansMiceSEMA6B protein, humanSema6b protein, mouseSemaphorinsCervical cancerHypoxiaMacrophage polarizationSemaphorin 6B

Identifiers

PMID40640851
PMCPMC12247440

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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.