miR-29a Promotes Lipid Droplet and Triglyceride Formation in HCV Infection by Inducing Expression of SREBP-1c and CAV1

Abstract

Aims: To examine the regulation of SREBP-1c and CAV1 by microRNA-29a (miR-29a) in cells infected with hepatitis C virus (HCV) in an attempt to control HCV-induced non-alcoholic fatty liver disease.Methods: In order to examine the manipulation of SREBP-1c and CAV1 by miR-29a, oleic acid (OA)-treated JFH-I-infected Huh-7 cells were used. OA was added 24 h post-transfection and gene expression was investigated by qRT-PCR at 48 h post treatment. The functional impact of the observed alteration in SREBP-1c and CAV1 expression was analyzed by examining lipid droplet (LD) and triglyceride (TG) content at 72 h post-OA treatment using light microscopy and spectrophotometry, respectively. Viral load was quantified by qRT-PCR at 72 h post-transfection.Results: OA treatment induced the expression of miR-29a and SREBP-1c, as compared to untreated cells. Forced miR-29a expression led to a significant up-regulation of SREBP-1c as well as CAV1 compared to mock untransfected cells. Ectopic expression of miR-29a resulted in a marked increase in LDs and their respective TGs, while miR-29a antagomirs decreased both the LD and TG content compared to mock untransfected cells. Moreover, forcing the expression of miR-29a in JFH-1 HCV-infected Huh-7 cells resulted in 53% reduction in viral titers compared to mock untransfected Huh-7 cells.Conclusion: Inducing miR-29a expression significantly induces SREBP-1c and CAV1 expression, thereby increasing LDs as well as their respective TGs. Nonetheless, forcing the expression of miR-29a resulted in reduction of HCV RNA levels in Huh-7 cells.

Caveolin1 protects against diet induced hepatic lipid accumulation in mice

“…Several studies have revealed that SREBP1 could bind to the sterol regulatory elements (SREs) in the CAV1 gene promoter and subsequently negatively regulate CAV1 expression [28,29]. One recent study supported this conception in which they found SREBP1 knockdown induced by siRNA resulted in a significant increase in CAV1 mRNA level [30]. The study reporting curcumin inhibits ox-LDL-induced cholesterol accumulation in cultured rat vascular smooth muscle cells (VSMC) through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP1 also supported the above findings [31].…”

<p>Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment</p>

“…It has been reported that genetic changes of Cav1 might modify the risk for breast cancer,151 and Cav1 acts both as a tumor suppressor as well as an oncogene, and plays a key role in breast cancer tumorigenesis 152. In addition to breast cancer carcinogenic process, Cav1 is also associated with lung cancer,153,154 colorectal cancer,155 gastric cancer,156,157 cervical cancer,158 hepatocellular carcinoma,159 pancreatic cancer,160 bladder cancer,161 pulmonary hypertension,162–164 virus infection,165,166 cardiovascular disease,167,168 diabetes mellitus,169 nanomedicines endocytosis170 and lipodystrophy 171. Besides, it has been reported that caveo-lin-2 (Cav2) can also mediate the initiation and development of breast cancer 26…”

Diagnostic biomarker and therapeutic target applications of miR‐326 in cancers: A systematic review

“…El-Ekiaby et al, 2012;N. M. El-Ekiaby et al, 2017;El Sobky et al, 2016;Estrabaud et al, 2015;Khanizadeh et al, 2017;Mahdy et al, 2016;Niu et al, 2016;Oksuz et al, 2015;Ono et al, 2017;Van Renne et al, 2017;G. Xu et al, 2014), influenza virus (Ingle et al, 2015;Y.…”