LncRNA CCAT1 functions as apoptosis inhibitor in podocytes via autophagy inhibition

Abstract

Podocyte apoptosis importantly contributes to various kidney diseases. Long noncoding RNAs Colon cancer‐associated transcript‐1 (CCAT‐1) has been demonstrated for a critical role in cell proliferation. In the present study, the relationship between CCAT1 and popdocyte impairment, and the underlying mechanism was investigated. Podocytes were isolated from mice and then treated with tumor necrosis factor‐α to simulate podocyte injury. After developed CCAT1 overexpression or knockdown, cell viabilities were determined with the CCK‐8 assay, apoptosis was examined with Flow cytometry, the autophagy was observed by Western blot. Furthermore, phosphorylated PI3K and Akt expressions were examined. We found that after CCAT1 overexpression, the cell viability was significantly increased, apoptosis was significantly decreased, and autophagy was significantly inhibited, which was indicated by induced P62, LC3B‐I and decreased LC3B‐II. In addition, CCAT1 overexpression induced the levels of phosphorylated PI3K and Akt. With Rap treatment, these effects by CCAT1 were reversed. Furthermore, the results contrary to the effects by CCAT1 overexpression were presented after CCAT1 knockdown, and this was inhibited by 3‐MA. Taken together, our results suggested that CCAT1 induction critically participated in apoptosis inhibition in podocytes through autophagy inhibition via increasing PI3K/Akt signaling. This might act as a promising therapeutic intervention for renal diseases associated with podocyte apoptosis.

The Preventive Effects and Mode of Actions of Ulva Fasciata Synthesized Silver Nanoparticles in Doxorubicin-Induced Hepatotoxicity in Wistar Rats

“…It is also worth mentioning here that stimulation of inflammation might give rise to trigger apoptosis [80]. In this regard, TNF-α may stimulate apoptosis via TNF receptor or death receptor, thereby activate the extrinsic pathway of apoptosis [81]. This elucidation is supported by the results of the present study which revealed that doxorubicin injection stimulates the expression of pro-apoptotic mediator in the intrinsic pathway of apoptosis (Fig.…”

“…fasciata. As p53 is an intermediate in the intrinsic pathway of apoptosis that was triggered by oxidative stress [5,81,116] and TNF-α triggers extrinsic apoptosis via cell death/TNF receptors [5], this led us to suggest that U. fasciata and AgNPs/U. fasciata may decrease apoptosis in doxorubicinadministered rats through affecting both intrinsic and extrinsic apoptotic pathways (Fig.…”

Morroniside Inhibits H2O2-Induced Podocyte Apoptosis by Down-Regulating NOX4 Expression Controlled by Autophagy In Vitro

“…Most studies suggest that autophagy plays a protective role in podocytes (Ye et al, 2019), but some scientists hold different views. Su et al (2020) have demonstrated that autophagy is involved in podocyte apoptosis caused by tumor necrosis factora (TNF-a), and some IncRNAs can exert anti-apoptotic effects via inhibiting autophagy. It is remarkable that podocyte apoptosis and autophagy activation often appear together.…”

Targeting autophagy to overcome drug resistance: further developments

“…LncRNA colon cancer-associated transcript-1 (CCAT1) is closely associated with a variety of cancers. A recent study has clearly shown that lncRNA CCTA1 induced autophagy inhibition for cell survival via increasing PI3K/AKT pathway in podocytes [ 110 ]. LINC00470, known as C18orf2, also activates AKT signaling, inhibits cell autophagy and promotes glioblastoma cell tumorigenesis and poor patient prognosis [ 111 ].…”