ArticleJournal of experimental & clinical cancer research : CR2019
RNA-binding protein KHSRP promotes tumor growth and metastasis in non-small cell lung cancer.
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 66 papers.
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Who cites it
66 citing papers in PubMed, 103 citations in OpenAlex.
- FUBP3 regulates expression and alternative splicing of genes associated with cell proliferation and apoptosis in cancer cells.Oncology letters · 2026Article
- Multiomics analysis identifies the prognostic significance and biological roles of the HNRNP family in lung adenocarcinoma.Discover oncology · 2026Article
- mFrontiers in cell and developmental biology · 2026Review
- Differences in the expression profiles of m6A-related genes and the prognostic role in immunotherapy for lung adenocarcinoma patients.Frontiers in oncology · 2026Article
- HHIPL2 positively governs Hedgehog signaling to accelerate non-small cell lung cancer progression via enhancing HNRNPC-mediated HNF1A mRNA stabilization.Cell death & disease · 2025Article
- Downregulation of KHSRP enhances carboplatin sensitivity in non-small cell lung cancer.Hereditas · 2025Article
- KHSRP promotes the malignant behavior and cisplatin resistance of bladder cancer cells through the CLASP2/MAPRE1 axis.The pharmacogenomics journal · 2025Article
- Targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 mScience advances · 2025Article
- RNA-binding proteins and autophagy in lung cancer: mechanistic insights and therapeutic perspectives.Discover oncology · 2025Review
- Androgen receptor-regulated lncRNA PRCAT71 promotes AR signaling through the interaction with KHSRP in prostate cancer.Science advances · 2025Article
- Role of NAT10-mediated acBMC pulmonary medicine · 2025Article
- FAM210B activates STAT1/IRF9/IFIT3 axis by upregulating IFN-α/β expression to impede the progression of lung adenocarcinoma.Cell death & disease · 2025Article
- Expanding the Functions of KHSRP Protein: Insights into DNA G-Quadruplex Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- KHSRP promotes cancer stem cell maintenance, tumorigenesis, and suppresses anti-tumor immunity in gastric cancer.Oncology research · 2025Article
- CircDONSON regulates the proliferation, invasion and migration of non-small cell lung cancer cells through the MAPK signaling pathway.Genes & diseases · 2025Article
- Article
- EFTUD2 is a promising diagnostic and prognostic indicator involved in the tumor immune microenvironment and glycolysis of lung adenocarcinoma.Frontiers in oncology · 2025Article
- The therapeutic potential of RNA m(6)A in lung cancer.Cell communication and signaling : CCS · 2024Review
- Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma.Frontiers of medicine · 2024Article
- Nucleic acid-binding KH domain proteins influence a spectrum of biological pathways including as part of membrane-localized complexes.Journal of structural biology: X · 2024Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundKH-type splicing regulatory protein (KHSRP) plays an important role in cancer invasion, but the relevant mechanism is not well known. In the present study, we investigated the function and potential molecular mechanism of KHSRP in non-small cell lung cancer (NSCLC) metastasis and elucidated its clinical significance.
methodsIsobaric tags for relative and absolute quantitation and the SWATH™ approach were combined with nanoliquid chromatography-tandem mass spectrometry analysis to identify metastasis-associated nucleoproteins in NSCLC. Real-time PCR and Western blot were used to screen for metastasis-associated candidate molecules. Gene knockdown and overexpression were used to investigate their functions and molecular mechanisms in lung cancer cells. Coimmunoprecipitation (Co-IP) experiments were performed to identify the interactions between candidate molecules and their interacting proteins. Gene expression and its association with multiple clinicopathologic characteristics were analyzed by immunohistochemistry (IHC) and Western blot in human lung cancer specimens.
resultsKHSRP was identified as a metastasis-associated candidate molecule. In NSCLC cell lines, knockdown of KHSRP significantly reduced lung cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas overexpression of KHSRP did the opposite. Mechanistically, the protein heterogeneous nuclear ribonucleoprotein C (C1/C2) (HNRNPC) was identified to interact with KHSRP using Co-IP experiments. In NSCLC cell lines, overexpression of HNRNPC significantly promoted lung cancer cell proliferation, migration, and invasion in vitro and in vivo. KHSRP and HNRNPC may induce human lung cancer cell invasion and metastasis by activating the IFN-α-JAK-STAT1 signaling pathway. Drastically higher expression levels of KHSRP and HNRNPC were observed in lung cancer tissues compared to those in adjacent noncancerous tissues. Increased KHSRP and HNRNPC expression was significantly associated with advanced tumor stages and metastasis (both lymph node and distant). Kaplan-Meier survival analysis showed that patients with high KHSRP and HNRNPC expression levels were predicted to have the shortest survival times and to have a poor prognosis.
conclusionsKHSRP plays an important role in NSCLC metastasis and may serve as a potential prognostic marker and novel therapeutic target for lung cancer metastasis treatment.
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