# Non-Coding RNA-Based Therapeutic Strategies in Triple-Negative Breast Cancer: A Systematic Review **Authors:** Giovana Prado Scaratti, Inaiê Maiala de Almeida Miranda, Emanuelle Nunes-Souza, Mayara Oliveira Ruthes, Daiane Rosolen, Aline Simoneti Fonseca, Luciane Regina Cavalli PMC · DOI: 10.3390/ijms27041882 · International Journal of Molecular Sciences · 2026-02-15 ## TL;DR This review explores how non-coding RNAs could offer new treatment options for triple-negative breast cancer, which currently lacks effective targeted therapies. ## Contribution The paper systematically identifies 28 ncRNAs as potential therapeutic targets in TNBC through pre-clinical studies from 2020 to 2025. ## Key findings - Modulating 28 specific ncRNAs suppressed tumor growth and inhibited metastasis in pre-clinical models. - ncRNA-based therapies restored sensitivity to standard chemotherapeutic agents in TNBC. - Advanced delivery systems like nanoparticles and exosomes were used to target ncRNAs effectively. ## Abstract Triple-negative breast cancer (TNBC) is characterized by marked clinical and molecular heterogeneity, which underlies the limited success of currently available targeted therapies and results in most patients relying on cytotoxic chemotherapy. This therapeutic gap underscores the pressing need for novel therapeutic approaches, in which non-coding RNAs (ncRNAs) have emerged as promising candidates. In this systematic review, 35 pre-clinical studies published between 2020 and 2025 were analyzed to evaluate the therapeutic potential of targeting ncRNAs in TNBC, including miRNAs, lncRNAs, and circRNAs. The original articles employed in vivo tumor models to assess the therapeutic response of ncRNA expression modulation, using miRNA mimics, antagomiRs, ASOs, shRNAs, and siRNAs integrated into advanced targeted delivery systems, such as nanoparticles and exosomes. According to the selected studies, 28 specific ncRNAs were identified as actionable molecular targets. Modulation of these molecules consistently resulted in tumor growth suppression, metastasis inhibition, and restoration of sensitivity to standard chemotherapeutic agents. Collectively, the pre-clinical evidence presented in these studies positions ncRNA-based therapies as innovative, promising, and potentially effective strategies for advancing TNBC treatment. ## Linked entities - **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989) ## Full-text entities - **Genes:** Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, Parp1 (poly (ADP-ribose) polymerase family, member 1) [NCBI Gene 11545] {aka 5830444G22Rik, ARTD1, Adprp, Adprt1, PARP, PPOL}, Tcf4 (transcription factor 4) [NCBI Gene 21413] {aka 5730422P05Rik, ASP-I2, E2-2, E2.2, ITF-2, ITF-2b}, Mir182 (microRNA 182) [NCBI Gene 387177] {aka Mirn182, mir-182, mmu-mir-182}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Slc29a1 (solute carrier family 29 (nucleoside transporters), member 1) [NCBI Gene 63959] {aka 1200014D21Rik, ENT1, mENT1}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, Tfdp2 (transcription factor Dp 2) [NCBI Gene 211586] {aka 1110029I05Rik, A330080J22Rik, DP-3, DP3}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Mir143 (microRNA 143) [NCBI Gene 387161] {aka Mirn143, mir-143, mmu-mir-143}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Itga5 (integrin alpha 5 (fibronectin receptor alpha)) [NCBI Gene 16402] {aka Cd49e, Fnra, VLA5}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, Atg5 (autophagy related 5) [NCBI Gene 11793] {aka 2010107M05Rik, 3110067M24Rik, Apg5l, Atg5l, Paddy}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, Sox8 (SRY (sex determining region Y)-box 8) [NCBI Gene 20681], Malat1 (metastasis associated lung adenocarcinoma transcript 1 (non-coding RNA)) [NCBI Gene 72289] {aka 2210401K01Rik, 9430072K23Rik, Neat2}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, Cdh1 (cadherin 1) [NCBI Gene 12550] {aka ARC-1, E-cad, Ecad, L-CAM, UVO, Um}, Mir10b (microRNA 10b) [NCBI Gene 387144] {aka Mirn10b, mir-10b, mmu-mir-10b}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Fas (Fas cell surface death receptor) [NCBI Gene 14102] {aka APO1, APT1, CD95, TNFR6, Tnfrsf6, lpr}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Slc2a1 (solute carrier family 2 (facilitated glucose transporter), member 1) [NCBI Gene 20525] {aka GT1, Glut-1, Glut1, M100200, Rgsc200}, Plau (plasminogen activator, urokinase) [NCBI Gene 18792] {aka u-PA, uPA}, Hnrnpd (heterogeneous nuclear ribonucleoprotein D) [NCBI Gene 11991] {aka Auf1, Hnrpd}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, Snai1 (snail family zinc finger 1) [NCBI Gene 20613] {aka Sna, Sna1, Snail, Snail1}, Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, Pten (phosphatase and tensin homolog) [NCBI Gene 19211] {aka 2310035O07Rik, A130070J02Rik, B430203M17Rik, MMAC1, PTENbeta, TEP1}, Chek1 (checkpoint kinase 1) [NCBI Gene 12649] {aka Chk1, rad27}, MIR22 (microRNA 22) [NCBI Gene 407004] {aka MIRN22, hsa-mir-22, miR-22}, Trp53 (transformation related protein 53) [NCBI Gene 22059] {aka Tp53, bbl, bfy, bhy, p44, p53}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Met (met proto-oncogene, receptor tyrosine kinase) [NCBI Gene 17295] {aka HGF, HGFR, Par4, c-Met}, Hk2 (hexokinase 2) [NCBI Gene 15277] {aka HKII}, Hoxd10 (homeobox D10) [NCBI Gene 15430] {aka Hox-4.5, Hox-5.3}, Zeb1 (zinc finger E-box binding homeobox 1) [NCBI Gene 21417] {aka 3110032K11Rik, AREB6, BZP, MEB1, Nil2, TCF-8}, Mir155 (microRNA 155) [NCBI Gene 387173] {aka Mirn155, mir-155, mmu-mir-155}, Ldha (lactate dehydrogenase A) [NCBI Gene 16828] {aka Ldh1, Ldhm, l7R2}, Mir34a (microRNA 34a) [NCBI Gene 723848] {aka Mirn34a, mir-34a, mmu-mir-34a}, Smad3 (SMAD family member 3) [NCBI Gene 17127] {aka Madh3}, Cdh2 (cadherin 2) [NCBI Gene 12558] {aka CDHN, N-CAD, Ncad}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Pdcd4 (programmed cell death 4) [NCBI Gene 18569] {aka D19Ucla1, Ma3, Tis}, Foxo1 (forkhead box O1) [NCBI Gene 56458] {aka Afxh, FKHR, Fkhr1, Foxo1a}, Mir326 (microRNA 326) [NCBI Gene 723840] {aka Mirn326, mir-326, mmu-mir-326}, Otub2 (OTU domain, ubiquitin aldehyde binding 2) [NCBI Gene 68149] {aka 2010015L18Rik, 4930586I02Rik, OTB2, OTU2}, Ptk2 (PTK2 protein tyrosine kinase 2) [NCBI Gene 14083] {aka FADK 1, FAK, FRNK, Fadk, p125FAK}, Pcna (proliferating cell nuclear antigen) [NCBI Gene 18538], Mettl14 (methyltransferase 14, N6-adenosine-methyltransferase subunit) [NCBI Gene 210529] {aka G430022H21Rik, mKIAA1627}, Dgcr8 (DGCR8, microprocessor complex subunit) [NCBI Gene 94223] {aka D16H22S1742E, D16H22S788E, D16Wis2, Gy1, N41, Vo59c07}, Foxg1 (forkhead box G1) [NCBI Gene 15228] {aka 2900064B05Rik, BF-1, Bf1, Hfh9, Hfhbf1} - **Diseases:** death (MESH:D003643), tumorigenic (MESH:D002471), liver metastasis (MESH:D009362), Inflammation (MESH:D007249), osteosarcoma (MESH:D012516), injury to (MESH:D014947), weight loss (MESH:D015431), cytotoxicity (MESH:D064420), cancer (MESH:D009369), lung cancer metastasis (MESH:D008175), tumorigenesis (MESH:D063646), TNBC cancer (MESH:D064726), Breast Cancer (MESH:D001943), SCID (MESH:D053632), necrosis (MESH:D009336), hepatocellular carcinoma (MESH:D006528), loss of body weight (MESH:D001835) - **Chemicals:** disulfide (MESH:D004220), Carboplatin (MESH:D016190), Zn+ (MESH:D015032), phosphorus (MESH:D010758), CS (MESH:D048271), silica (MESH:D012822), DOX (MESH:D004317), garcinol (MESH:C054597), mannose (MESH:D008358), H&E (MESH:D006371), gold (MESH:D006046), pyro (MESH:C040298), curcumin (MESH:D003474), doxycycline (MESH:D004318), PEI-SPDP-Man (-), CB1954 (MESH:C100099), cetuximab (MESH:D000068818), poly (epsilon-caprolactone (MESH:C016240), beta-cyclodextrin (MESH:C031215), amino acid (MESH:D000596), PEG (MESH:D011092), PEI (MESH:D011094), paclitaxel (MESH:D017239), (ethylene glycol (MESH:D019855), GCV (MESH:D015774), MOF (MESH:D000073396), ASOs (MESH:D016376), polysaccharide (MESH:D011134), Nucleotides (MESH:D009711), Apt (MESH:C071989), omacetaxine mepesuccinate (MESH:D000077863), Man (MESH:D008353), glutathione (MESH:D005978), gemcitabine, oxaliplatin (MESH:C508870), ATP (MESH:D000255), L+ (MESH:D007930), ROS (MESH:D017382), HA (MESH:D006820), calcium (MESH:D002118), oxaliplatin (MESH:D000077150), oxiplatin (MESH:C431073), GEM (MESH:D000093542), oligonucleotide (MESH:D009841), PBS (MESH:D007854), PLGA (MESH:D000077182) - **Species:** Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Vesicular stomatitis virus (species) [taxon 11276] - **Cell lines:** MDA-MB-436 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0623), BT-549 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_1092), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), HCC1806 — Homo sapiens (Human), Breast acantholytic squamous cell carcinoma, Cancer cell line (CVCL_1258), MDA-MB-157 — Homo sapiens (Human), Breast carcinoma, Cancer cell line (CVCL_0618) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12940445/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940445/full.md ## References 117 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940445/full.md --- Source: https://tomesphere.com/paper/PMC12940445