HAPLN3 inhibits apoptosis and promotes EMT of clear cell renal cell carcinoma via ERK and Bcl-2 signal pathways

Abstract

Hyaluronan and proteoglycan link protein 3 (HAPLN3) is a member of the hyaluronan and proteoglycan link protein family expressed in the extracellular matrix closely associated with the development and occurrence of various malignant tumors; yet, its function in clear cell renal cell cancer (ccRCC) is still poorly understood. The following study investigated the progress and mechanism of HAPLN3 on ccRCC using bioinformatics analysis and in vitro experiments. In order to determine whether HAPLN3 is differentially expressed in ccRCC, we analyzed data from the Cancer Genome Atlas (TCGA) and GSE40435 and further validated them in the Human Protein Atlas (HPA) database. Simultaneously, the TCGA dataset was utilized to study the relationship between HAPLN3 expression and the progression of ccRCC and its prognostic value in ccRCC. Gene enrichment analysis (GSEA) was used to explore HAPLN3-related signaling pathways in ccRCC. The TIMER database investigates the link for both HAPLN3 and immune cell in ltration. Different ccRCC cell lines the role of HAPLN3 on cell biological behavior in vitro. HAPLN3 was increased in ccRCC, and its high expression was related to the patients' survival rates and clinical characteristics. GSEA showed that HAPLN3 is mainly enriched in proliferative and metastatic pathways. In addition, HAPLN3 was an independently associated signi cant predictor in patients with ccRCC. Functional experiments demonstrated that HAPLN3 could promote the proliferation, migration, and invasion of ccRCC cells through the ERK1/2 signaling pathway. To sum up, our data suggest that HAPLN3 may serve as a new prognostic biomarker and potential therapeutic target for ccRCC.

Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

“…ROS can both promote and suppress metastasis, suggesting that the mechanism by which ROS affect cancers is dependent on multiple observational conditions [39]. Thus, to determine whether HBB is a factor in cancer exacerbation, various molecular groups related to tumor exacerbation (Bcl-2 family and cadherins) should be examined as described previously [40]. Additionally, it is necessary to reconstruct clinical results using animal experiments to reach comprehensive conclusions on HBB function.…”

Hyaluronic Acid Interacting Molecules Mediated Crosstalk between Cancer Cells and Microenvironment from Primary Tumour to Distant Metastasis

“…Pancreas cancer [107], malignant pleural mesothelioma [108], lung cancer [109] Colorectal cancer [110], malignant gliomas [111] HAPLN2 Malignant gliomas [111] HAPLN3 Breast cancer [112,113], clear cell renal cell cancer [114] Advanced skin cutaneous melanoma [115], cutaneous melanoma [116] Gene methylation: prostate cancer [117] and de novo metastatic prostate cancer [118] HAPLN4 Malignant gliomas [111]…”

“…Certain HAIMs, including CD44, TSG-6, LYVE-1, RHAMM, HAPLN3, NCAN, and VCAN, can facilitate the proliferation of cancer cells [57,85,100,114,155,[183][184][185][186][187][188][189]. CD44 is essential for the rapid growth of various cancer cells [183].…”

“…HAPLN3 acts as an oncogenic factor in cells, and a loss of HAPLN3 hinders the ability of clear cell renal cell carcinoma (ccRCC) cells to proliferate, migrate, and invade by suppressing activation of ERK1/2 [114]. NCAN is mainly expressed in the nervous system and works as an inhibitory molecule to inhibit axon regeneration following a nerve injury [51], but acts as a promoter for the proliferation of neuroblastoma cells [129].…”

“…HAPLN3 enhances the migration and infiltration of ccRCC cells by activating the ERK1/2 pathway [114]. Both HAPLN3 and HAPLN4 can enhance the migration of glioma cells, while HAPLN4 can strengthen the mitogenic effect of BCAN [111].…”