The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.     

LncRNA SNHG1 regulates immune escape of renal cell carcinoma by targeting miR-129-3p to activate STAT3 and PD-L1

Immune escape of renal cell carcinoma (RCC) impacts patient survival. However, the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in RCC immune escape remains unclear. Quantitative real-time PCR and western blotting results revealed that the expression of lncRNA SNHG1 and STAT3 were upregulated in RCC tissues and cells and that the expression of miR-129-3p was downregulated. Enzyme-linked immunosorbent assay results revealed the increased levels of immune-related factors (interferon-γ, tumour necrosis factor α, and interleukin-2) in RCC tissues. SNHG1 knockdown or miR-129-3p overexpression inhibited the proliferation and invasion of A498 and 786-O cells, while the proliferation and cytotoxicity of CD8⁺ T cells increased, which promoted the secretion of immune-related factors. STAT3 overexpression decreased the protective effect of miR-129-3p overexpression on RCC cell immune escape. In addition, miR-129-3p knockdown and STAT3 overexpression decreased the protective effect of lncRNA SNHG1 knockdown on RCC cell immune escape. In addition, PD-L1 expression was downregulated after lncRNA SNHG1 knockdown but upregulated after miR-129-3p knockdown and STAT3 overexpression. Dual-luciferase assays showed that lncRNA SNHG1 targets miR-129-3p, and miR-129-3p targets STAT3. RNA pull-down and RNA immunoprecipitation assays verified the regulatory relationship between SNHG1 and STAT3. In vivo, shSNHG1 prolonged the overall survival of RCC tumour model mice and inhibited RCC tumour growth and immune escape but increased CD8⁺ T cell infiltration in mice. Our findings provide an experimental basis for elucidating the molecular mechanisms of immune escape by RCC and reveal a novel target to treat this disease.     

Long noncoding RNA SNHG15 promotes human breast cancer proliferation,migration and invasion by sponging miR-211-3p

Long non-coding RNAs (lncRNA) have been demonstrated to act as essential regulators in the development and progression of breast cancer. In our study, we found that long noncoding RNA SNHG15 was highly expressed in breast cancer tissues and cell lines. And the expression of SNHG15 was correlated with TNM stage, lymphnode metastasis and survival in breast cancer patients. SNHG15 knockdown significantly inhibited the proliferation and induced apoptosis in breast cancer cells in vitro and in vivo. Besides, SNHG15 downregulation suppressed cell migration and invasion in MCF-7 and BT-20 cells, and inhibited epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG15 acted as a competing endogenous RNA to sponge miR-211-3p, which was downregulated in breast cancers and inhibited cell proliferation and migration. Our results showed that there was a negative correlation between SNHG15 and miR-211-3p expression in breast cancer patients. Collectively, we, for the first time, revealed the functions of SNHG15 and miR-211-3p in breast cancer.     

LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR-128/CD151 pathway in hepatocellular carcinoma

Dysregulation of long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and tumor progression, including hepatocellular carcinoma (HCC). Small nucleolar RNA host gene 3 (SNHG3) has been considered as an lncRNA to be associated with a poor prognosis in patients with HCC. Here, we reported that SNHG3 expression was significantly higher in the highly metastatic HCC (HCCLM3) cells compared with the lowly metastatic HCC cells (Hep3B and PLC/PRF/5). Furthermore, forced expression of SNHG3 promoted cell invasion, epithelial-mesenchymal transition (EMT), and sorafenib resistance in HCC. Moreover, SNHG3 overexpression induced HCC cells EMT via miR-128/CD151 cascade activation. Clinically, our data revealed that increased SNHG3 expression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that SNHG3 may be a novel therapeutic target and a biomarker for predicting response to sorafenib treatment of HCC.     

Exosome-mediated lncRNA SNHG11 regulates angiogenesis in pancreatic carcinoma through miR-324-3p/VEGFA axis

Pancreatic carcinoma (PC) is one of the most common and deadly human malignancies worldwide. LncRNAs play significant roles in the occurrence and development of various cancers. LncRNA SNHG11 (SNHG11) has been found to display high expression in serum of PC patients, which implies that dysregulated SNHG11 may be related to the development of PC. However, there is still a knowledge gap concerning the specific function and molecular mechanism of SNHG11 in PC. After conducting experiments with constructed models in vitro or in vivo, we found that exosomal SNHG11 promoted cell proliferation, migration, and angiogenesis but impeded cell apoptosis in PC in vitro, and additionally, it facilitated tumor growth in vivo. Exosome-mediated SNHG11 regulated the expression of VEGFA through sponging miR-324-3p. Rescue assays validated that the inhibitory effect of SNHG11 depletion on cell proliferation, migration, and angiogenesis could be reversed by miR-324-3p downregulation or VEGFA upregulation, and the promoting effect of SNHG11 silence on cell apoptosis could be rescued by transfection of miR-324-3p inhibitor or pcDNA3.1-VEGFA. To conclude, exosomal-mediated SNHG11 could regulate PC progression via miR-324-3p/VEGFA axis. Our findings may provide a novel insight for understanding PC, which might contribute to the development of potential PC biomarker.     

LncRNA SNHG12 promotes proliferation and epithelial mesenchymal transition in hepatocellular carcinoma through targeting HEG1 via miR-516a-5p

Hepatocellular carcinoma (HCC) is the most common cancer and its prognosis is poor due to metastasis and recurrence. EMT is associated with metastasis. A deep understanding of regulatory mechanism of EMT is critical. LncRNA is involved in regulation of various biological processes including EMT. This study aimed to investigate the regulatory signal axis among lncRNA SNHG12, miR-516a-5p and the target gene HEG1 during EMT. Cell cycle and apoptosis were analyzed by flow cytometry. Tumorigenesis was analyzed by clone formation assay. Wound healing assay and transwell assay was performed to detect migration and invasion, respectively. Interaction among SNHG12, miR-516a-5p and HEG1 were analyzed by dual luciferase assay and RIP assay. We also detected expression of RNA and protein by QPCR and western blotting. Finally, tumor growth was analyzed by tumorigenesis assay in vivo. Ki-67 and HEG1 level in tumor tissues was analyzed by IHC. SNHG12 and HEG1 were upregulated, miR-516a-5p was downregulated in HCC cell lines. SNHG12 could interact with and inhibit miR-516a-5p. MiR-516a-5p could interact with HEG1 and inhibit HEG1 expression. Knock down SNHG12 inhibited proliferation, migration, invasion, EMT and promoted apoptosis of HCC cells. Such effects were antagonized by inhibiting miR-516a-5p. SNHG12 overexpression lead to opposite results. Similar results were observed in mice. SNHG12 could promote EMT in HCC through targeting and inhibiting miR-516a-5p, which eventually upregulated HEG1 expression, in both cell and mice.     

LncRNA SNHG20 contributes to cell proliferation and invasion by upregulating ZFX expression sponging miR-495-3p in gastric cancer

Long noncoding RNAs (lncRNAs) exert key regulators in cancer development and progression. The functional significance of lncRNA small nucleolar RNA host gene 20 (SNHG20) was reported in gastric cancer (GC); however, the underlying molecular mechanism in GC development is largely unknown. Here, our results showed that the lncRNA SNHG20 expression was significantly higher in GC tissues compared with adjacent normal tissues by quantitative real-time PCR (qRT-PCR) analysis. Higher lncRNA SNHG20 expression was highly associated with tumor size and lymphatic metastasis of patients. Patients with higher lncRNA SNHG20 expression predicted a short disease-free survival (DFS) and overall survival (OS). Furthermore, lncRNA SNHG20 expression negatively associated with miR-495-3p expression and regulated miR-495-3p expression. Function assays confirmed that lncRNA SNHG20 knockdown using RNA interference suppressed cell proliferation and invasion of GC by negatively regulating miR-495-3p expression. Moreover, we demonstrated that lncRNA SNHG20 inhibited zinc finger protein X-linked (ZFX) expression by negatively miR-495-3p expression in GC cells. In vivo, the current study also indicated that lncRNA SNHG20 knockdown reduced the tumor growth by downregulating ZFX expression. Thus, our results implied that inhibition of SNHG20/miR-495-3p/ZFX axis may provide valuable target for GC treatment.     

SNHG16 as the miRNA let-7b-5p sponge facilitates the G2/M and epithelial-mesenchymal transition by regulating CDC25B and HMGA2 expression in hepatocellular carcinoma

Long noncoding RNAs (lncRNAs) play crucial roles in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of small nucleolar RNA host gene 16 (SNHG16) for regulating the cell cycle and epithelial to mesenchymal transition (EMT) remain elusive. In this study, SNHG16 expression profiles of HCC tissues or cell lines were compared with those of normal tissues or hepatocyte cell line. The effect of SNHG16 knockdown in HCC cell lines was investigated by using in vitro loss-of-function experiments and in vivo nude mouse experiments. The potential molecular regulatory mechanism of SNHG16 in HCC progression was investigated by using mechanistic experiments and rescue assays. The results revealed that SNHG16 was highly expressed in HCC tissues and cell lines, which predicted poor prognosis of HCC patients. On one hand, the downregulation of SNHG16 induced G2/M cell cycle arrest, inducing cell apoptosis and suppression of cell proliferation. On the other hand, it inhibited cell metastasis and EMT progression demonstrated by in vitro loss-of-function cell experiments. Besides, knockdown of SNHG16 increased the sensitivity of HCC cells to cisplatin. For the detailed mechanism, SNHG16 was demonstrated to act as a let-7b-5p sponge in HCC. SNHG16 facilitated the G2/M cell cycle transition by directly acting on the let-7b-5p/CDC25B/CDK1 axis, and promoted cell metastasis and EMT progression by regulating the let-7b-5p/HMGA2 axis in HCC. In addition, the mechanism of SNHG16 for regulating HCC cell proliferation and metastasis was further confirmed in vivo by mouse experiments. Furthermore, these results can provide new insights into HCC treatment and its molecular pathogenesis, which may enlighten the further research of the molecular pathogenesis of HCC.     

The function of SNHG7/miR-449a/ACSL1 axis in thyroid cancer

Thyroid cancer (TC) has been characterized as the most common malignant malady of the endocrine system. Small nucleolar RNA host gene 7 (SNHG7) has been reported to serve as a key regulator in a large number of human cancer types, but its role in TC and the underlying regulatory mechanism have never been evaluated yet. The present study indicated that the expression of SNHG7 was markedly higher in TC cell lines. Knockdown of SNHG7 led to a suppression of TC cell progression and migration. Acyl-CoA synthetase long-chain family member 1 (ACSL1) has also been demonstrated as an oncogene in many cancers. Herein an inhibition of ACSL1 after SNHG7 knockdown was captured. Further, the suppressing effects of SNHG7 knockdown on TC cell processes were counteracted by ACSL1 overexpression. Data from online bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays validated the interaction between microRNA-449a (miR-449a) and SNHG7 or ACSL1. It was also verified that SNHG7 sequestered miR-449a and therefore elevated ACSL1 expression levels. To conclude, the current study indicated that SNHG7 promoted proliferation and migration of TC cells by sponging miR-449a and therefore upregulating ACSL1. The present study may provide more explorations about the molecular regulation mechanism of long noncoding RNAs in TC progression.     

LINC01433 promotes hepatocellular carcinoma progression via modulating the miR-1301/STAT3 axis

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR-1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull-down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR-1301, and it was shown that miR-1301 mimics significantly suppressed STAT3 in HCC cells. Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR-1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR-1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment.     

lncRNA SNHG3 facilitates acute myeloid leukemia cell growth via the regulation of miR-758-3p/SRGN axis

Small nucleolar RNA host gene 3 (SNHG3) is a newly identified long non-coding RNA whose dysregulation has been reported in several cancers. However, the details about clinical significances and biological functions of SNHG3 on acute myeloid leukemia (AML) remain covered. In this study, we revealed increased SNHG3 expression in AML samples and cells and its high potential as a prognostic biomarker for AML patients. Likewise, serglycin (SRGN), which plays an important role in granule-mediated apoptosis, was previously verified to be upregulated in AML and confirmed again by the present study, and its upregulation predicted poor outcomes in AML. Furthermore, knockdown of SNHG3 or SRGN inhibited cell proliferation and induced cell apoptosis. Besides, silencing SNHG3 noticeably decreased the expression of SRGN in AML cells. Moreover, we uncovered that SNHG3 modulated SRGN expression by competitively binding with miR-758-3p. Importantly, both miR-758-3p suppression and SRGN overexpression could mitigate the inhibitory effects of SNHG3 depletion on AML cell growth. Intriguingly, the higher SRGN expression in AML samples with a higher SNHG3 level exhibited an enhanced Ki67 level but a reduced caspase 3 level. To sum up, SNHG3 elicits a growth-promoting function in AML via sponging miR-758-3p to regulate SRGN expression, providing a new therapeutic road for AML patients.     

Retracted: In vivo and in vitro effects of microRNA-221 on hepatocellular carcinoma development and progression through the JAK–STAT3 signaling pathway by targeting SOCS3

Hepatocellular carcinoma (HCC), as the third leading cancer-caused deaths, prevails with high mortality, and affects more than half a million individuals per year worldwide. A former study revealed that microRNA-221 (miR-221) was involved in cell proliferation of liver cancer and HCC development. The current study aims to evaluate whether miR-221 targeting SOCS3 affects HCC through JAK–STAT3 signaling pathway. A series of miR-221 mimic, miR-221 inhibitor, siRNA against SOCS3, and SOCS3 plasmids were introduced to SMMC7721 cells with the highest miR-221 expression assessed. The expression of JAK–STAT3 signaling pathway–related genes and proteins was determined by Western blot analysis. Cell apoptosis, viability, migration, and invasion were evaluated by means of flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, and transwell assays, respectively. HCC xenograft in nude mice was performed to measure HCC tumor growth. miR-221 was found to be highly expressed but SOCS3 was poorly expressed in HCC tissues. miR-221 expression was correlated with lymph node metastasis (LNM) and tumor node metastasis (TNM) of HCC, and SOCS3 expression was correlated with LNM, differentiation and TNM of HCC. SOCS3 is a target gene of miR-221. MiR-221 mimic or si-SOCS3 exposure was found to induce cell viability, migration, and invasion, and reduce apoptosis. MiR-221 inhibitor was observed to have inhibitory effects on HCC cell proliferation, migration, and invasion. Moreover, the expression of JAK–STAT3 signaling pathway was suppressed by miR-221 inhibitor. Downregulated miR-221 expression could promote its target gene SOCS3 to inhibit the proliferation, invasion and migration of HCC cells by repressing JAK–STAT3 signaling pathway.