Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases.

Autophagy in the proximal tubules may promote fibrosis by activating tubular cell death, interstitial inflammation, and the production of pro-fibrotic factors. The signal transducer and activator of transcription 3 (STAT3) is activated as a potential transcription factor, which mediates the stimulation of renal fibrosis. We investigated the role of the STAT3 in autophagy and its effect on the prevention of interstitial renal fibrosis. In this study, we use synthesized STAT3 decoy oligonucleotides (ODN), which were injected into the tail veins of unilateral ureteral obstruction (UUO) mice, to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and collagen were decreased by STAT3 decoy ODN. The autophagy markers microtubule-associated protein light chain 3 (LC3) and fibronectin, were identified through immunofluorescent staining, indicating that they were reduced in the group injected with ODN. The expressions of LC3, Beclin1, p62, and autophagy-related 5–12 (Atg5–12) and hypoxia inducible factor-1α (HIF-1α) were inhibited in the ODN injection group. We determined the inhibitory effect of autophagy in chronic kidney disease and confirmed that STAT3 decoy ODN effectively inhibited autophagy by inhibiting the expression of STAT3 transcription factors in the UUO group.

Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated.

Liver damage caused by various factors results in fibrosis and inflammation, leading to cirrhosis and cancer. Fibrosis results in the accumulation of extracellular matrix components. The role of STAT proteins in mediating liver inflammation and fibrosis has been well documented; however, approved therapies targeting STAT3 inhibition against liver disease are lacking. This study investigated the anti-fibrotic and anti-inflammatory effects of STAT3 decoy oligodeoxynucleotides (ODN) in hepatocytes and liver fibrosis mouse models. STAT3 decoy ODN were delivered into cells using liposomes and hydrodynamic tail vein injection into 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice in which liver injury was induced. STAT3 target gene expression changes were verified using qPCR and Western blotting. Liver tissue fibrosis and bile duct proliferation were assessed in animal experiments using staining techniques, and macrophage and inflammatory cytokine distribution was verified using immunohistochemistry. STAT3 decoy ODN reduced fibrosis and inflammatory factors in liver cancer cell lines and DDC-induced liver injury mouse model. These results suggest that STAT3 decoy ODN may effectively treat liver fibrosis and must be clinically investigated.

Secretory carcinoma of the salivary gland (SC) is a newly introduced rare salivary gland tumor that shares histological, immunohistochemical, and genetic characteristics with secretory carcinoma of the breast. Here, we report the cytologic features of two cases of SC confirmed by surgical resection. In these two cases, SC was incidentally detected in a 64-year-old female and a 56-yearold male. Fine needle aspiration cytology revealed nests of tumor cells with a papillary or glandular structure floating in mucinous secretions. The tumor cells demonstrated uniform, round, smooth nuclear contours and distinct nucleoli. Multiple characteristic cytoplasmic vacuoles were revealed. Singly scattered tumor cells frequently showed variable sized cytoplasmic vacuoles. The cytopathologic diagnosis of SC should be considered when characteristic cytological findings are revealed. Further immunohistochemistry and gene analyses are helpful to diagnose SC.