Table 1 Role of RBPs in tumors
RBP | The basic mechanism of RBPs regulation | Tumor type | Established target | Up- or downregulation | Model or cells | Mechanism/signaling pathway/conclusion | Biological functions | Refs |
|---|---|---|---|---|---|---|---|---|
TRBP | mRNA translation, mRNA stability | Breast carcinomas, colorectal cancer, endometrial cancer | Amyloid precursor protein (APP), ZNF395 | Up- or downregulation | Human colorectal and endometrial cancer cell lines | PKR pathway | Promotes or inhibits cell proliferation and invasion | |
hnRNP E1 | mRNA transcription, mRNA stability, mRNA transport, alternative RNA splicing | Human hepatoma cell, melanoma, breast cancer | PNUTS, miR-205 | Downregulation | Clinical specimens of human hepatocellular carcinoma (HCC) A549 MDA-MB-231 | The deletion of hnRNP E1 in liver cancer contributes to the formation of metastatic phenotype. hnRNPE1 impedes the shearing of lncRNA-PNUTS, thereby inhibiting tumor cell migration, invasion, and metastasis. | Inhibits cell proliferation, invasion, and metastasis EMT | |
hnRNPL | Alternative RNA splicing | Prostate cancer | CTBP1, ROR2, STX3 | Upregulation | CRISPR Cas9-LNCaP, CWR22Rv1, DU145, and PC3 cells | HNRNPL regulates circular RNA formation in human prostate cancer. | Promotes cell proliferation, invasion, and metastasis | [23] |
hnRNP A1/A2 | Alternative RNA splicing | Glioma, breast cancer, hepatocellular carcinoma | PK-M1/M2, SIRT1, SIRT6, let-7a, c-Myc, Stat3 | Upregulation | Glioma xenograft model, breast cancer clinical samples, HepG2 cells stably expressing hnRNP A1 or 4KR | Let-7a/c-Myc/hnRNPA1/PKM2 signaling. Let-7a-5p/Stat3/hnRNP-A1/PKM2 signaling pathway. Sirtuin-mediated deacetylation of hnRNP A1 inhibits HCC cell proliferation and tumorigenesis in a PKM2-dependent manner. | Promotes apoptosis, proliferation, migration, and invasion | |
hnRNPK | mRNA transcription, mRNA translation | Non-small-cell lung cancer | MAP 1B-LC1 | Upregulation | NSCLC clinical samples, adjacent non-tumor tissues | Interaction of hnRNP K with MAP 1B-LC1 promotes TGF-β-mediated EMT in lung cancer cells. | Promotes proliferation, EMT | [27] |
hnRNPC | Alternative RNA splicing | Breast cancer, gastric cancer | RIG-I, 5B2 | Upregulation | Constructed CRISPR/Cas9-hnRNPC MCF7 and T47D cell lines; gastric cancer cell lines resistant to 5-fluorouracil (5FU), paclitaxel (TA), and cisplatin (DDP) | Inhibition of HNRNPC prevented the proliferation and tumorigenesis of MCF7 and T47D and activated the type I interferon response. HNRNPC as a candidate biomarker for chemoresistance in gastric cancer | Promotes proliferation, tumorigenesis | |
HuR | subcellular localization, mRNA stability, mRNA translation | Gastric cancer, breast cancer, colon cancer, lung cancer, varian cancer | CCNA1/B1/E1, MDM2, MYC, PTMA, SIRT1, SNAIL, VEGF | Upregulation | Clinical samples of various tumor tissues MDA-MB-231, MCF-7, H1299, A549, MRC-9, CCD16 | HuR is usually activated through the PI3K/AKT/NF-kB pathway. Circ-HuR serves as a tumor suppressor to inhibit CNBP-facilitated HuR expression and gastric cancer progression. MiR-155-5p controls the migration of colon cancer cells through HuR post-transcriptional regulation. Integrin β1/FAK/ERK signaling | Exerts proliferation anti-apoptotic effects | |
ZEB1 | mRNA stability | Multiple tumors | CCR2, CCL2, miR-200, miR-203, MMPs, CDH1, IL6IL8, PDL1, INK4A/B, MSRB3 | Upregulation | Mouse models and human samples | ZEB1 has a pleiotropic effect in cancer, promoting the dynamic process of reversible transformation of tumor cells between metastable states. | Foster EMT, stemness, invasiveness | |
RBM38 | mRNA stability, mRNA translation, post-transcriptional regulation, mRNA splicing | Colorectal cancer, acute myeloid leukemia, renal cell carcinoma, hepatocellular carcinoma | PTEN, ZO-1, STARD13, CDH5, HOXD10, HOXD1, CDKN1A, LATS2 P53, Mdm2 | Downregulation | Cell lines and clinical samples of various tumors | The potential tumor suppressor gene RBM38 has been identified in various tumors. | Inhibit EMT, stemness, invasiveness | |
PTBP3 | Alternative RNA splicing, mRNA stability, RNA transport, RNA translation, RNA decay | Hepatocellular carcinoma, breast cancer, gastric cancer | NEAT1, pre-miR-612, ZEB1, CAV1 | Upregulation | Human HCC tissues, gastric cancer cells (MKN45 and SGC7901) Clinical samples MCF-7, MDA-MB-453/231 | PTBP3 regulates the balance of splicing variants (NEAT1_1, NEAT1_2, and miR-612) in HCC. PTBP3 as a regulator of EMT that acts by governing expression of ZEB1. PTBP3 may regulate CAV1 through alternative splicing and become a metastasis gene for gastric cancer. | Promoted HCC cell proliferation and metastasis both in vitro and in vivo regulation EMT | |
PTBP1 | RNA transport, RNA translation | Acute myeloid | FLT3 | Upregulation | FLT3-ITD-positive cells, FLT3-ITD-negative cells | circMYBL2 regulates FLT3 translation by recruiting PTBP1 to promote FLT3-ITD AML progression. | Promotes proliferation and differentiation | [49] |
NELFE | mRNA stability, RNA translation | Hepatocellular carcinoma | MYC-related genes, SYNGR2 | Upregulation | Clinical HCC samples | NELFE is an oncogenic protein that causes imbalance in the HCC transcriptome by regulating MYC signaling. | Promoted HCC cell proliferation and metastasis | [50] |
LIN28 | mRNA transcription, mRNA translation | Multiple tumors | Let-7 family members, PD-L1 | Upregulation | Clinical samples of various tumor tissues | Crosstalk between LIN28A/LIN28B and let-7 loops and certain oncogenes (such as MYC, RAS, PI3K/AKT, NF-κB, and β-catenin) to regulate the characteristics of cancer. LIN28/let-7/PD-L1 pathway | Poor prognosis, increased cellular proliferation | |
HNRNPU | Alternative RNA splicing, mRNA stability, mRNA metabolism mRNA transport | Neuroblastoma | HNF4A-AS1, CTCF | Upregulation | MCF 10A, HEK293T, NB cell lines | HNF4A-AS1/hnRNPU/CTCF axis | Promote aerobic glycolysis and NB progress |