Abstract:Background
Accumulating evidences have been reported that long noncoding RNAs play crucial roles in the progression of hepatocellular carcinoma (HCC). SnoRNA host gene 6 (SNHG6) is believed to be involved in several human cancers, but the specific molecular mechanism of SNHG6 in HCC is not well studied.
Methods
In this study, we experimentally down-regulated the SNHG6 in two hepatocellular carcinoma cell lines in vitro, and then measured the prolif… Show more
“…LncRNA can mechanically act as a competing endogenous RNA (ceRNA) and bind with miRNAs to inhibit the effect of miRNA on their target mRNAs. SNHG6 promotes G1/S-phase transition in HCC by impairing miR-204-5p-mediated inhibition of E2F1 (Chen et al 2021 ) and promotes the progression of HCC by targeting miR-6509-5p and HIF1A (Fan et al 2021 ). In addition to combining with miRNAs, lncRNA has also been reported to be able to bind to proteins and affect their function.…”
Metabolic reprogramming is an important feature in tumor progression. Long noncoding RNA’s (lncRNA) small nucleolar RNA host gene 6 (SNHG6) acts as a proto-oncogene in hepatocellular carcinoma (HCC) but its role in glycolysis is mostly unknown. The role of SNHG6 and Block of proliferation 1 (BOP1) on glycolysis is assessed by glucose uptake, lactate production, oxygen consumptive rate (OCR) and extracellular acidification rate (ECAR) and glycolytic enzyme levels. The regulatory effect of SNHG6 on BOP1 protein was confirmed by Western blotting, MS2 pull-down, RNA pull-down, and RIP assay. SNHG6 and BOP1 levels were increased in HCC tissues and cells. SNHG6 and BOP1 were prognostic factors in HCC patients and significantly correlated to TP53 mutant and tumor grade. SNHG6 promoted proliferation, inhibited apoptosis, enhanced glucose uptake and lactate production, decreased OCR, and increased ECAR in HCC cell lines. SNHG6 could bind the BOP1 protein and enhance its stability. BOP1 overexpression rescued the change of proliferation, apoptosis, and glycolysis in HCCLM3 and SMMC-7721 cells. Our data indicate that SNHG6 accelerates proliferation and glycolysis and inhibits the apoptosis of HCC cell lines by binding the BOP1 protein and enhancing its stability. Both SNHG6 and BOP1 are promising prognostic and therapeutic markers in HCC.
“…LncRNA can mechanically act as a competing endogenous RNA (ceRNA) and bind with miRNAs to inhibit the effect of miRNA on their target mRNAs. SNHG6 promotes G1/S-phase transition in HCC by impairing miR-204-5p-mediated inhibition of E2F1 (Chen et al 2021 ) and promotes the progression of HCC by targeting miR-6509-5p and HIF1A (Fan et al 2021 ). In addition to combining with miRNAs, lncRNA has also been reported to be able to bind to proteins and affect their function.…”
Metabolic reprogramming is an important feature in tumor progression. Long noncoding RNA’s (lncRNA) small nucleolar RNA host gene 6 (SNHG6) acts as a proto-oncogene in hepatocellular carcinoma (HCC) but its role in glycolysis is mostly unknown. The role of SNHG6 and Block of proliferation 1 (BOP1) on glycolysis is assessed by glucose uptake, lactate production, oxygen consumptive rate (OCR) and extracellular acidification rate (ECAR) and glycolytic enzyme levels. The regulatory effect of SNHG6 on BOP1 protein was confirmed by Western blotting, MS2 pull-down, RNA pull-down, and RIP assay. SNHG6 and BOP1 levels were increased in HCC tissues and cells. SNHG6 and BOP1 were prognostic factors in HCC patients and significantly correlated to TP53 mutant and tumor grade. SNHG6 promoted proliferation, inhibited apoptosis, enhanced glucose uptake and lactate production, decreased OCR, and increased ECAR in HCC cell lines. SNHG6 could bind the BOP1 protein and enhance its stability. BOP1 overexpression rescued the change of proliferation, apoptosis, and glycolysis in HCCLM3 and SMMC-7721 cells. Our data indicate that SNHG6 accelerates proliferation and glycolysis and inhibits the apoptosis of HCC cell lines by binding the BOP1 protein and enhancing its stability. Both SNHG6 and BOP1 are promising prognostic and therapeutic markers in HCC.
“…In the past 10 years, lncRNA has become a topic of intense interest in cancer research. LncRNAs play important roles in HCC by regulating cell proliferation, migration, and invasion [23][24][25]. The lncRNA LIMT has been identified as a novel and critical regulator in breast cancer [17].…”
Background
The long non-coding RNA LIMT (lncRNA inhibiting metastasis) acts as a tumor suppressor factor in some cancers. However, the biological role of LIMT in hepatocellular carcinoma (HCC) has not been explored.
Methods and Results
Quantitative real-time PCR was performed to evaluate the expression of LIMT in HCC tissue. The effects of LIMT on tumor growth and metastasis were assessed by in vitro experiments, including colony formation and transwell assays, and in vivo in nude mouse models. Western blot analysis was used to evaluate the expression levels of proteins associated with epithelial-mesenchymal transition (EMT). LIMT expression was significantly lower in HCC than in normal liver tissue. Functionally, overexpression of LIMT repressed the proliferation, invasion, and EMT of HCC cells, while LIMT knockdown increased proliferation, invasion, and EMT of HCC cells in vitro. Furthermore, LIMT overexpression suppressed HCC growth and metastasis while silencing of LIMT had an opposite effect in vivo. Finally, LIMT overexpression reversed EGF-induced EMT.
Conclusions
Our results suggest that LIMT could play an anti-cancer effect in HCC and might be a potential novel therapeutic target in HCC.
“…Numerous studies have shown that cancer progression is fostered by SNHG6 [ 170 , 171 , 172 , 173 ]. Moreover, SNHG6 can elevate the expression of HIF-1α by either sponging miRNAs or enhancing the translation of HIF-1α mRNA [ 150 , 151 , 152 ].…”
“…As a consequence, SNHG6 enhances migration and invasion abilities of hepatocellular carcinoma cells, along with an increase in HIF-1α expression. In xenografts, the growth of hepatocellular carcinoma is suppressed by the downregulation of SNHG6 [ 151 ] ( Figure 2 and Table 2 ).…”
Hypoxia is one of the representative microenvironment features in cancer and is considered to be associated with the dismal prognosis of patients. Hypoxia-driven cellular pathways are largely regulated by hypoxia-inducible factors (HIFs) and notably exert influence on the hallmarks of cancer, such as stemness, angiogenesis, invasion, metastasis, and the resistance towards apoptotic cell death and therapeutic resistance; therefore, hypoxia has been considered as a potential hurdle for cancer therapy. Growing evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated in cancer and take part in gene regulatory networks owing to their various modes of action through interacting with proteins and microRNAs. In this review, we focus attention on the relationship between hypoxia/HIFs and lncRNAs, in company with the possibility of lncRNAs as candidate molecules for controlling cancer.
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