MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

Abstract

Background/Aims: MiR-30a-5p, a member of the microRNA-30 family (miR-30), is known to function as a tumor suppressor in several different cancers. However, the expression levels, biological function, and underlying mechanisms of miR-30a-5p in renal cell carcinoma (RCC) remain unclear. Glucose-regulated protein78 (GRP78) is a common cancer biomarker and promotes the growth and survival of cancer cells. The expression of GRP78 has been reported to be modulated by miR-30a in neurons. In this study, the expression profile of miR-30a-5p in clear cell renal cell carcinoma (ccRCC) and its effect on ccRCC through regulating GRP78 expression was investigated. Methods: MiR-30a-5p expression was analyzed using bioinformatic software on open microarray datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and confirmed by quantitative RT-PCR (qRT-PCR) in ccRCC cell lines. Cell proliferation was investigated using CCK-8 and cell count assays. Western blotting, immunohistochemistry, luciferase reporter assays, and flow cytometry were employed to investigate the mechanisms of the effect of miR-30a-5p on ccRCC Results: MiR-30a-5p was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. MiR-30a-5p was found to both suppress the growth of ccRCC cells and promote apoptosis of ccRCC cells in vitro. GRP78 was the direct target gene of miR-30a-5p, and the GRP78 expression was inversely correlated with the expression of miR-30a-5p in vivo and in vitro. The functional studies of GRP78 overexpression or knockdown demonstrated that GRP78 promoted proliferation and anti-apoptosis of ccRCC cells, and the oncogenic activity of GRP78 resulting in by miR-30a-5p overexpression. Conclusion: MiR-30a-5p is a bona fide negative regulator of GRP78 expression, and the anti-tumor activity of miR-30a-5p in ccRCC is due at least in part to down-regulating GRP78 expression and modulating the unfolded protein response (UPR) pathway. Thus, miR-30-GRP78 interaction provides a novel therapeutic candidate target in ccRCC treatment.

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis

“…The host miR-30 family (five members, consisting of miR30a to miR30e) plays important roles in cancers and viral infections (30,34,36,37). We recently reported that miR-30a-5p, a member of the miR-30 family, is downregulated and that is expression is inversely correlated with the levels of ER stress in renal cancer, indicating that ER stress might inhibit miR-30a-5p expression (34). To assess whether ER stress suppresses the expression of miR-30a-5p, we initially analyzed the levels of miR-30a-5p in swine testicular (ST) cells following treatment with the ER stress inducer thapsigargin (Tg).…”

Urinary exosome miR‐30c‐5p as a biomarker of clear cell renal cell carcinoma that inhibits progression by targeting HSPA5

“…A number of studies have demonstrated the function that HSPA5 plays in cancer metastasis and in anti‐apoptotic process of cancer cells . HSPA5 expression positively correlates with the large tumour size, aggressiveness, high clinical stage and resistance to conventional chemotherapy of RCC . Additionally, several studies have focused on the regulation mechanism or signalling pathway of the differential expression of HSPA5 in cancers.…”

“…25 HSPA5 expression positively correlates with the large tumour size, aggressiveness, high clinical stage and resistance to conventional chemotherapy of RCC. 26 Additionally, several studies have focused on the regulation mechanism or signalling pathway of the differential expression of HSPA5 in cancers. Chang et al found that when E1A was expressed in cancer cells, p300 was activated to reduce acetylated HSPA5 levels and enhance its binding to GP78, thereby promoting HSPA5 ubiquitination and the subsequent inhibition of metastasis.…”

Identification and Validation of Two Novel Prognostic lncRNAs in Kidney Renal Clear Cell Carcinoma

“…Researchers have demonstrated that the 5-year survival rate of KIRC patients is less than 10% [27]. In the past, great efforts have been made to provide insights into the molecular mechanisms underlying KIRC, but the focus has been on protein-coding genes or miRNA [28,29]. Therefore, understanding the molecular mechanism of KIRC may provide clinicians with new treatment strategies for this disease.…”