The regulation of LRPs by miRNAs in cancer: influencing cancer characteristics and responses to treatment

Abstract

The low-density lipoprotein receptor-related protein (LRP) family is a group of cell surface receptors that participate in a variety of biological processes, including lipid metabolism, Wnt signaling, and bone metabolism. miRNAs are small non-coding RNA molecules that regulate gene expression and play a role in many biological processes, including the occurrence and development of tumors. Accumulating evidence demonstrates that LRP members are modulated by miRNAs across multiple cancer types, influencing key oncogenic processes-including tumor cell proliferation, apoptosis suppression, extracellular matrix remodeling, cell adhesion, and angiogenesis. The LRPs, miRNAs, their upstream lncRNAs, and downstream signaling molecules often form complex signaling pathways to regulate the activity of tumor cells. However, the tissue-specific roles and mechanistic underpinnings of these pathways remain incompletely understood. When examining the emerging concept of the interaction between miRNAs and LRPs, we emphasize the significance of these complex regulatory layers in the initiation and progression of cancer. Collectively, these findings are critical for advancing our understanding of the role of the LRPs family in the occurrence and development of tumors, as well as for the development of new strategies for cancer treatment.

Keywords: Cancer; CircRNAs; LRPs; LncRNA; miRNA.

Fig. 1

The miRNA/LRPSs axis in Colorectal cancer. (A) Under various stress conditions, LRP1, p53, and miR-103/107 constitute a feedback regulatory loop, modulating the apoptosis of colorectal cancer cells. Oncogenic lncRNAs and circRNAs repress miR-103/107, thereby enhancing LRP1 expression. (B) LRP6, miR-92, and DKK3 form a positive feedback loop in colorectal cancer, synergistically with oncogenic lncRNAs, to promote LRP6 expression. This enhancement facilitates increased invasion, metastasis, and chemoresistance

Fig. 2

The miRNA/LRPSs axis in Pancreatic cancer. (A) OIP5-AS1 upregulates LRP1 expression by inhibiting miR-429, thus augmenting invasion, metastasis, and chemoresistance in pancreatic cancer. (B) H19 enhances LRP5/6 expression by suppressing miR-194, leading to increased proliferation and migration in pancreatic cancer

Fig. 3

The miRNA/LRPSs axis in Hepatocellular cancer. (A) LncRNAs stimulate the expression of LRP4 by suppressing miR-455-5p, which in turn promotes cell proliferation, metastasis, and cell cycle progression in hepatocellular carcinoma. (B) Multiple miRNAs have been identified to negatively regulate LRP6 in hepatocellular carcinoma. Oncogenic lncRNAs and circRNAs counteract these miRNAs, increasing LRP6 expression and thereby promoting cell proliferation, invasion, metastasis, migration, and angiogenesis

Fig. 4

The miRNA/LRPSs axis in Gastric cancer. (A) SNHG20 promotes LRP4 expression by suppressing miR-140-5p, enhancing proliferation, invasion, and migration in gastric cancer. (B) SBF2-AS1 enhances LRP5 expression by inhibiting miR-545, thereby promoting proliferation, invasion, EMT, and drug resistance in gastric cancer

Fig. 5

The miRNA/LRPSs axis in breast cancer. miRNAs exert an inhibitory effect on the expression of LRP6, thereby impeding breast cancer progression. Conversely, lncRNAs can counteract the suppressive function of these miRNAs by downregulating their expression, leading to enhanced tumor proliferation, invasion, and migration in breast cancer

Fig. 6

The miRNA/LRPSs axis in thyroid carcinoma. (A) IQCH-AS1 upregulates the expression of LRP1B by suppressing miR-196a-5p, consequently promoting proliferation, invasion, and migration in thyroid carcinoma. (B) LncRNAs stimulate the expression of LRP4 by inhibiting miR-429, thereby enhancing tumor proliferation, invasion, and migration in thyroid carcinoma (C) In hepatocellular carcinoma, miRNAs have been identified to negatively regulate LRP6. Furthermore, the circRNA Circ_0011373 can inhibit miR-127, leading to increased LRP6 expression and promoting cell proliferation, invasion, migration, and EMT

Fig. 7

The miRNA/LRPSs axis in melanoma. LINC00662 promotes the expression of LRP1 by suppressing miR-107, which in turn enhances proliferation, invasion, metastasis, and drug resistance in melanoma

Fig. 8

The miRNA/LRPSs axis in glioblastoma. reduce apoptosis in glioblastoma. (A) miR-429 inhibits the expression of LRP1, which can induce proliferation, migration, and survival of glioblastoma cells, while reducing apoptosis. (B) Tumor suppressor miRNAs in glioblastoma exert their inhibitory function on cancer progression by inhibiting LRP6. Oncogenic lncRNAs, on the other hand, augment LRP6 expression by suppressing these miRNAs, thereby inducing cell proliferation, tumorigenesis, EMT, invasion, and chemotherapy resistance, and reducing apoptosis in glioblastoma