LncRNA AWPPH and miRNA-21 regulates cancer cell proliferation and chemosensitivity in triple-negative breast cancer by interacting with each other

Long–non-coding RNAs (lncRNA) AWPPH promotes the progression of liver and bladder cancer, indicating its oncogenic role. The current study aimed to explore the involvement of AWPPH in triple-negative breast cancer (TNBC). In the current study, we found that plasma levels of lncRNA AWPPH and microRNA-21 (miRNA-21) were upregulated in patients with TNBC than in healthy controls, and the upregulation of plasma lncRNA AWPPH and miRNA-21 distinguished early-stage patients with TNBC from healthy controls. Plasma levels of lncRNA AWPPH and miRNA-21 were significantly and positively correlated in both patients with TNBC and healthy controls. LncRNA AWPPH and miRNA-21 overexpression led to promoted cancer cells proliferation and improved cancer cell viability under carboplatin treatment, while lncRNA AWPPH small interfering RNA (siRNA) silencing played an opposite role. In addition, miRNA-21 overexpression attenuated the effects of lncRNA AWPPH siRNA silencing on of cancer cell behaviors. LncRNA AWPPH overexpression led to upregulated miRNA-21 in TNBC cells, while miRNA-21 overexpression also led to significantly upregulated lncRNA AWPPH expression. Therefore, lncRNA AWPPH and miRNA-21 may regulate cancer cell proliferation and chemosensitivity in TNBC by interacting with each other.     

Long noncoding RNA HAND2-AS1 inhibits cancer cell proliferation,migration, and invasion in esophagus squamous cell carcinoma by regulating microRNA-21

Long noncoding RNA (lncRNA) HAND2-AS1 is a well-characterized tumor suppressor in several types of malignancies, while its role in esophagus squamous cell carcinoma (ESCC) is unknown. In this study, we found that lncRNA HAND2-AS1 was downregulated, while microRNA-21 ( miRNA-21) was upregulated in tumor tissues than in adjacent healthy tissues of ESCC patients. Expression levels of lncRNA HAND2-AS1 and miRNA-21 were significantly and inversely correlated in tumor tissues but not in healthy tissues. Plasma levels of lncRNA HAND2-AS1 were lower in ESCC patients than in healthy controls, and downregulation of plasma lncRNA HAND2-AS1 distinguished early stage ESCC patients from healthy controls. lncRNA HAND2-AS1 overexpression resulted in downregulation of miRNA-21 in cells of ESCC cell lines and inhibited cell proliferation, migration, and invasion. miRNA-21 overexpression failed to affect lncRNA HAND2-AS1 expression but significantly attenuated the inhibitory effect of lncRNA HAND2-AS1 overexpression on cancer cell proliferation, migration, and invasion. Therefore, lncRNA HAND2-AS1 may inhibit cancer cell proliferation, migration, and invasion in ESCC by regulating miRNA-21.     

LncRNA CASC11 improves atherosclerosis by downregulating IL-9 and regulating vascular smooth muscle cell apoptosis and proliferation

LncRNA CASC11 is an oncogene in several types of cancer, while its role in atherosclerosis is unknown. In the present study we found that CASC11 was downregulated, while IL-9 was upregulated in plasma of atherosclerosis patients compared with healthy controls. Altered plasma levels of CASC11 and IL-9 distinguished atherosclerosis patients from healthy controls. CASC11 and IL-9 were significantly and inversely correlated in atherosclerosis patients but not in healthy controls. Exogenous IL-9 treatment failed to significantly affect expression levels of CASC11 in vascular smooth muscle cells (VSMC), while CASC11 overexpression resulted in the downregulation of IL-9. CASC11 overexpression also resulted in the downregulation of proliferation and promoted apoptosis of VSMC. Therefore, CASC11 may improve atherosclerosis by downregulating IL-9 and regulating VSMC apoptosis and proliferation.     

LncRNA CASC11 promoted gastric cancer cell proliferation,migration and invasion in vitro by regulating cell cycle pathway

In this study, we aimed to investigate the effects of lncRNA CASC11 on gastric cancer (GC) cell progression through regulating miR-340-5p and cell cycle pathway. Expressions of lncRNA CASC11 in gastric cancer tissues and cell lines were determined by qRT-PCR. Differentially expressed lncRNAs, mRNAs and miRNAs were screened through microarray analysis. The relationship among CASC11, CDK1 and miR-340-5p was predicted by TargetScan and validated through dual luciferase reporter assay. Western blot assay examined the protein level of CDK1 and several cell cycle regulatory proteins. GO functional analysis and KEGG pathway analysis were used to predict the association between functions and related pathways. Cell proliferation was determined by CCK-8 assays. Cell apoptosis and cell cycle were detected by flow cytometry assay. CASC11 was highly expressed in GC tissues and cell lines. Knockdown of CASC11 inhibited GC cell proliferation, promoted cell apoptosis and blocked cell cycle. KEGG further indicated an enriched cell cycle pathway involving CDK1. QRT-PCR showed that miR-340-5p was down-regulated in GC cells tissues, while CDK1 was up-regulated. Furthermore, CASC11 acted as a sponge of miR-340-5p which directly targeted CDK1. Meanwhile, miR-340-5p overexpression promoted GC cell apoptosis and induced cell cycle arrest, while CDK1 overexpression inhibited cell apoptosis and accelerated cell cycle. Our study revealed the mechanism of CASC11/miR-340-5p/CDK1 network in GC cell line, and suggested that CASC11 was a novel facilitator that exerted a biological effect by activating the cell cycle signaling pathway. This finding provides a potential therapeutic target for GC.     

Overexpression of lncRNA snaR is correlated with progression and predicts poor survival of laryngeal squamous cell carcinoma

Long noncoding RNAs (lncRNA) snaR is a characterized oncogenic lncRNA in triple negative breast cancer and ovarian cancer, while its role in other human diseases is unknown. In the present study, we found that plasma levels of snaR were upregulated in patients with laryngeal squamous cell carcinoma (LSCC) than in healthy controls. Plasma levels of snaR increased with increase in AJCC stages. Follow-up study showed that high plasma levels of snaR were correlated with poor overall survival. Plasma levels of snaR were positively correlated with transforming growth factor beta (TGF-β1) in patients with LSCC but not in healthy controls. Overexpression of snaR resulted in upregulation of TGF-β1 in cells of human LSCC cell lines, while exogenous TGF-β1 treatment showed no significant effect on snaR expression. snaR overexpression and exogenous TGF-β1 treatment promoted LSCC cell proliferation, migration, and invasion. In addition, TGF-β inhibitor partially reduced the enhancing effects of snaR overexpression on LSCC cell proliferation, migration, and invasion. Therefore, overexpression of lncRNA snaR is correlated with progression and predicts poor survival of LSCC and the mechanism of its actions is likely related to TGF-β1.     

LncRNA NKILA inhibits the proliferation and promotes the apoptosis of CSCC cells by downregulating miRNA-21

Long noncoding RNA (lncRNA) NKILA has been well studied in several types of human tumors as a tumor suppressor, while its involvement in cervical squamous cell carcinoma (CSCC) remains unclear. In our studies, we found that serum NKILA was at lower levels and serum microRNA-21 (miRNA-21) was at higher levels in patients with early stage CSCC than in the healthy female. Altered expression of NKILA and miRNA-21 can effectively separate patients with CSCC at an early stage from healthy controls. Serum levels of NKILA were significantly and negatively correlated with miRNA-21 in patients with CSCC but not in normal controls. Overexpression of NKILA mediated the inhibited expression of miRNA-21 in CSCC cells, but mimic transfection of miRNA-21 did not significantly change the expression level of NKILA. Overexpression of NKILA repressed the proliferation and promoted the apoptosis of CSCC cells, while miRNA-21 showed opposite functions. In addition, miRNA-21 mimic transfection reduced the effects of NKILA on CSCC cells. Collectively, lncRNA NKILA could repress the proliferation and promote the apoptosis of CSCC cells by downregulating miRNA-21.     

LncRNA POU3F3 promotes proliferation and inhibits apoptosis of cancer cells in triple-negative breast cancer by inactivating caspase 9

It has been reported that lncRNA POU3F3 was upregulated in esophageal squamous-cell carcinomas, indicating its role as an oncogene in this disease. However, the mechanism of its function and its involvement in other malignancies is unknown. In the present study we found that expression levels of lncRNA POU3F3 were higher in tumor tissues than in adjacent healthy tissues of triple negative breast cancer (TNBC) patients and were significantly and inversely correlated with levels of cleaved caspase 9 only in tumor tissues. In addition, plasma levels of lncRNA POU3F3 were higher in TNBC patients than in healthy controls and were significantly and inversely correlated with levels of cleaved caspase 9 only in TNBC patients. In addition, treatment of exogenous Cleaved Caspase-9 significantly attenuated the effects of lncRNA POU3F3 overexpression on cancer cell proliferation and apoptosis. lncRNA POU3F3 may promote proliferation and inhibit apoptosis of cancer cells in triple-negative breast cancer.     

LncRNA PTCSC3 inhibits triple-negative breast cancer cell proliferation by downregulating lncRNA H19

Long noncoding RNA (lncRNA) PTCSC3 (hereafter PTCSC3 is used to represent lncRNA PTCSC3) inhibits glioma and thyroid cancer, indicating its potential tumor suppression function in other types of cancers. We explored the potential involvement of PTCSC3 in triple-negative breast cancer (TNBC). In the current study, we found that PTCSC3 was downregulated in tumor tissues of patients with TNBC. PTCSC3 expression was positively correlated with plasma levels of PTCSC3. LncRNA H19 was upregulated and was inversely correlated with PTCSC3 in tumor tissues. PTCSC3 overexpression led to downregulated H19 in TNBC cells, while H19 overexpression did not affect PTCSC3 expression. PTCSC3 inhibited and H19 promoted proliferation of TNBC cells. H19 overexpression attenuated the effects of PTCSC3 overexpression. Cancer cell migration and invasion were not significantly affected by PTCSC3 overexpression. Therefore, lncRNA PTCSC3 inhibits TNBC cell proliferation by downregulating lncRNA H19.     

LncRNA PAPAS promotes hepatocellular carcinoma by interacting with miR-188-5p

It has been observed that long noncoding RNA (lncRNA) PAPAS regulates rRNA synthesis, but its role in human diseases is unclear. Our study was carried out to investigate the role of PAPAS in hepatocellular carcinoma (HCC). In the present study, we found that PAPAS was upregulated both in plasma from patients with HCC and tumors compared with plasma from healthy people and tumor-adjacent healthy tissues. Expression levels of PAPAS in tumor tissues and plasma of patients with HCC were significantly and positively correlated. Plasma levels of PAPAS effectively distinguished stage I patients from healthy controls. MicroRNA (miR)-188-5p was downregulated in tumor tissues than in tumor-adjacent healthy tissues of patients with HCC, and was inversely correlated with PAPAS in tumor tissues but not in adjacent healthy tissues. PAPAS and miR-188-5p downregulated each other. PAPAS overexpression promoted, while miR-188-5p overexpression inhibited the HCC cell proliferation. Rescue experiment showed that miR-34a overexpression attenuated the effects of PAPAS overexpression. However, PAPAS overexpression failed to affect significantly cancer cell migration and invasion. Therefore, lncRNA PAPAS promotes HCC by interacting with miR-188-5p.     

lncRNA TUC338 is a potential diagnostic biomarker for bladder cancer

Although long noncoding RNA TUC338 has been characterized as an oncogene, its role in bladder cancer is unknown. The purpose of the present study is to investigate the function of TUC338 in bladder cancer. We found that TUC338 was upregulated in early-stage bladder cancer patients and showed early diagnostic values. After surgical resection, plasma levels of TUC338 were significantly downregulated. Moreover, microRNA 10b (miR-10b) was also upregulated in bladder cancer patients. TUC338 and miR-10b were positive and significantly correlated in bladder cancer patients, but not in healthy controls. Bladder cancer cells with TUC338 overexpression showed upregulated miR-10b, while miR-10b overexpression failed to significantly affect TUC338. TUC338 and miR-10b overexpression significantly promoted bladder cancer cell invasion and migration. Therefore, TUC338 may promote bladder cancer at least partially by upregulating miR-10b.     

Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a

Objectives

Long non‐coding RNA cancer susceptibility candidate 2 (CASC2) is a novel lncRNA and has been indicated as playing tumour suppressor gene in several tumours. However, the role of CASC2 in osteosarcoma is still uncovered.

Materials and methods

The CASC2 and miR‐181a expressions were measured via qRT‐PCR. CCK‐8 assay and colony formation assay were performed to determine the cell growth, and transwell assay was performed to assess the cell invasion.

Results

We showed that CASC2 expression was downregulated in osteosarcoma samples and cell lines. Moreover, we showed that downregulated expression of CASC2 was correlated with advanced TNM stage. Furthermore, overexpression of CASC2 inhibited osteosarcoma cell proliferation, colony formation, and invasion. In addition, we indicated that ectopic expression of CASC2 suppressed miR‐181a expression and enhanced the expression of Ras association domain family member 6 (RASSF6), PTEN and ATM in osteosarcoma cell, which were the direct target gene of miR‐181a. Moreover, we indicated that RASSF6 expression was downregulated in osteosarcoma samples and cell lines and downregulated expression of RASSF6 was correlated with advanced TNM stage. We found that the expression of RASSF6 was positively correlated with the expression of CASC2 in osteosarcoma tissues. Ectopic expression of CASC2 suppressed the osteosarcoma cell proliferation, colony formation and invasion through regulating RASSF6 expression.

Conclusions

Our data illuminated that CASC2 acted as a tumour suppressor in osteosarcoma progression.     

RNPC1 inhibits non-small cell lung cancer progression via regulating miR-181a/CASC2 axis

Objectives

To study the roles and mechanisms of RNA binding protein RNPC1 in non-small cell lung cancer progression.

Results

RNPC1 and long non-coding RNA CASC2 expression levels were significantly downregulated in lung cancer tissues compared with normal adjacent tissues, and their expression levels were positively correlated. Functionally, overexpression of RNPC1 or CASC2 inhibited non-small cell lung cancer cells proliferation, migration and invasion, and promoted cells apoptosis. Mechanistically, RNPC1 was found to harbor binding sites on CASC2 and directly bound to CASC2, and increased CASC2 mRNA stability and expression. Notably, the promotive effects of RNPC1 on CASC2 expression were attenuated by miR-181a overexpression. Moreover, CASC2 3′UTR with mutated miR-181a binding sites did not respond to RNPC1 alteration. Finally, the inhibitory effects of RNPC1 overexpression were attenuated or even reversed by CASC2 knockdown or miR-181a overexpression.

Conclusions

RNA bind protein RNPC1 could inhibit non-small cell lung cancer progression by competitively binding to CASC2 with miR-181a.

     

lncRNA MIR503HG functioned as a tumor suppressor and inhibited cell proliferation,metastasis and epithelial-mesenchymal transition in bladder cancer

Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss-of-function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial-mesenchymal transition-related mRNA and protein levels of ZEB1, Snail, N-cadherin, and vimentin, with an increase in E-cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.     

Retracted: LncRNA MT1JP functions as a tumor suppressor via regulating miR-214-3p expression in bladder cancer

Growing evidence suggested that the long noncoding RNAs (lncRNAs) regulate several pathophysiological processes in tumorigenesis and may be new biomarkers for tumor therapy. In this study, we studied the expression and role of lncRNA MT1JP in the development of bladder cancer. We demonstrated that the expression of MT1JP was downregulated in bladder tumor samples and cell lines. Ectopic expression of MT1JP suppressed cell proliferation, cycle, and invasion in bladder cancer. In addition, our result suggested that miR-214-3p overexpression decreased the luciferase activity of wild-type MT1JP but not mutated-type MT1JP and elevated expression of MT1JP decreased miR-214-3p expression in the bladder cancer cell. Furthermore, we indicated that the expression of miR-214-3p was upregulated in bladder tumor samples and cell lines. Ectopic expression of miR-214-3p promoted cell proliferation, cycle, and invasion in bladder cancer. MT1JP suppressed cell proliferation, cycle, and invasion via negative modulation of miR-214-3p in bladder cancer. These data suggested that lncRNA MT1JP acts a tumor suppressor gene in bladder cancer progression, considering MT1JP as a new therapeutic target in bladder cancer.     

Long noncoding RNA LINC-PINT is inhibited in gastric cancer and predicts poor survival

Long noncoding RNA (lncRNA) LINC-PINT expression is inhibited in many types of cancer cells, suggesting its role as a tumor suppressor. However, the functionality of LINC-PINT in gastric cancer and the clinical values are unknown. In the present study, we found that lncRNA LINC-PINT was downregulated, while microRNA-21 (miR-21) was upregulated in tumor tissues than in adjacent healthy tissues of gastric cancer patients. A significant and inverse correlation between expression levels of lncRNA LINC-PINT and miR-21 was found in both tumor tissues and adjacent healthy tissues. The low expression level of LINC-PINT and high expression level of the miR-21 tumor were correlated with poor prognosis. LINC-PINT overexpression casued miR-21 inhibition in cells of human gastric cancer cell lines, while miR-21 overexpression did not alter LINC-PINT expression. LINC-PINT overexpression led to inhibited, while miR-21 overexpression led to promoted proliferation, migration, and invasion of gastric cancer cells. Effects of LINC-PINT overexpression on cellular behaviors of gastric cancer cells were attenuated by miR-21 overexpression. Therefore, LINC-PINT may participate in gastric cancer through the crosstalk with miR-21.