Knockdown of lncRNA ZFAS1-suppressed non–small cell lung cancer progression via targeting the miR-150-5p/HMGA2 signaling

Non–small cell lung cancer (NSCLC) is the main type of lung malignancy. Early diagnosis and treatments for NSCLC are far from satisfactory due to the limited knowledge of the molecular mechanisms regarding NSCLC progression. Long noncoding RNA (lncRNA) ZNFX1 antisense RNA1 (ZFAS1) has been implicated for its functional role in the progression of malignant tumors. This study aimed to determine the ZFAS1 expression from lung cancer clinical samples and to explore the molecular mechanisms underlying ZFAS1-modulated NSCLC progression. Experimental assays revealed that clinical samples and cell lines of lung malignant tumors showed an upregulation of ZFSA1. ZFAS1 expression was markedly upregulated in the lung tissues from patients with advanced stage of this malignancy. The loss-of-function assays showed that knockdown of ZFAS1-suppressed NSCLC cell proliferative, as well as invasive potentials, increased NSCLC cell apoptotic rates in vitro and also attenuated tumor growth of NSCLC cells in the nude mice. Further experimental evidence showed that ZFAS1 inversely affected miR-150-5p expression and positively affected high-mobility group AT-hook 2 (HMGA2) expression in NSCLC cell lines. MiR-150-5p inhibition or HMGA2 overexpression counteracted the effects of ZFAS1 knockdown on NSCLC cell proliferative, invasive potentials and apoptotic rates. In light of examining the clinical lung cancer samples, miR-150-5p expression was downregulated and the HMGA2 expression was highly expressed in the lung cancer tissues compared with normal ones; the ZFAS1 expression showed a negative correlation with miR-150-5p expression but a positive correlation with HMGA2 expression in lung cancer tissues. To summarize, we, for the first time, demonstrated the inhibitory effects of ZFAS1 knockdown on NSCLC cell progression, and the results from mechanistic studies indicated that ZFAS1-mediated NSCLC progression cells via targeting miR-150-5p/HMGA2 signaling.     

The long noncoding RNA ZFAS1 promotes the progression of glioma by regulating the miR-150-5p/PLP2 axis

Numerous studies have reported that long noncoding RNA (lncRNA) dysregulation is involved in the progression of many malignant tumors, including glioma. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) plays an oncogenic role in various malignant tumors, such as gastric cancer and hepatocellular carcinoma. However, the underlying molecular mechanism of ZFAS1 in glioma has not been fully clarified. In this study, we found that the expression of ZFAS1 was upregulated in both glioma tissues and cell lines. Functional experiments revealed that ZFAS1 promoted glioma proliferation, migration and invasion, and increased resistance to temozolomide in vitro. By using online databases, RNA pull-down assays and luciferase reporter assays, ZFAS1 was demonstrated to act as a sponge of miR-150-5p. Furthermore, proteolipid protein 2 (PLP2) was shown to be the functional target of miR-150-5p. Rescue experiments revealed that ZFAS1 regulated the expression of PLP2 by sponging miR-150-5p. Finally, a xenograft tumor assay demonstrated that ZFAS1 promoted glioma growth in vivo. Our results showed that ZFAS1 promoted glioma malignant progression by regulating the miR-150-5p/PLP2 axis, which may provide a potential therapeutic target for the treatment of glioma.     

HOXC13-AS promotes breast cancer cell growth through regulating miR-497-5p/PTEN axis

Dysregulated long noncoding RNAs (lncRNAs) remains to be explored in tumorigenesis. LncRNA HOXC13 antisense RNA (HOXC13-AS) has been found as an oncogene in many cancers; however, the role of HOXC13-AS in breast cancer still elusive. In this study, the HOXC13-AS levels and its role in cell proliferation was first measured by real-time quantitative polymerase chain reaction, Cell Counting Kit-8 assay, and colony formation assay. It showed that HOXC13-AS was increased in breast cancer tissues compared with the adjacent normal tissues and upregulated HOXC13-AS promoted the growth of breast cancer cells. Then, we found that the miR-497-5p levels were downregulated in cancer tissues compared with the adjacent tissues and miR-497-5p suppressed breast cancer cell proliferation. Further study showed that HOXC13-AS could function as a “sponge” for miR-497-5p then suppress miR-497-5p expression. Moreover, we next identified that Phosphatase and Tensin homolog (PTEN) is the target of miR-497-5p. Overexpression of miR-497-5p by chemical mimics decreased the expression of PTEN, while downregulation of miR-497-5p by HOXC13-AS rescued the expression of PTEN. Finally, we showed that HOXC13-AS promoted the proliferation of breast cancer cells and tumor growth through miR-497-5p/PTEN axis in vitro and in vivo. Hence, we conclude that HOXC13-AS, which is significantly upregulated in breast cancers, promoted cell proliferation through the suppressed miR-497-5p and further upregulated PTEN.     

Inhibition of the long non-coding RNA ZFAS1 attenuates ferroptosis by sponging miR-150-5p and activates CCND2 against diabetic cardiomyopathy

Diabetic cardiomyopathy (DbCM) is responsible for increased morbidity and mortality in patients with diabetes and heart failure. However, the pathogenesis of DbCM has not yet been identified. Here, we investigated the important role of lncRNA-ZFAS1 in the pathological process of DbCM, which is associated with ferroptosis. Microarray data analysis of DbCM in patients or mouse models from GEO revealed the significance of ZFAS1 and the significant downregulation of miR-150-5p and CCND2. Briefly, DbCM was established in high glucose (HG)–treated cardiomyocytes and db/db mice to form in vitro and in vivo models. Ad-ZFAS1, Ad-sh-ZFAS1, mimic miR-150-5p, Ad-CCND2 and Ad-sh-CCND2 were intracoronarily administered to the mouse model or transfected into HG-treated cardiomyocytes to determine whether ZFAS1 regulates miR-150-5p and CCND2 in ferroptosis. The effect of ZFAS1 on the left ventricular myocardial tissues of db/db mice and HG-treated cardiomyocytes, ferroptosis and apoptosis was determined by Masson staining, immunohistochemical staining, Western blotting, monobromobimane staining, immunofluorescence staining and JC-1 staining. The relationships among ZFAS1, miR-150-5p and CCND2 were evaluated using dual-luciferase reporter assays and RNA pull-down assays. Inhibition of ZFAS1 led to reduced collagen deposition, decreased cardiomyocyte apoptosis and ferroptosis, and attenuated DbCM progression. ZFAS1 sponges miR-150-5p to downregulate CCND2 expression. Ad-sh-ZFAS1, miR-150-5p mimic, and Ad-CCND2 transfection attenuated ferroptosis and DbCM development both in vitro and in vivo. However, transfection with Ad-ZFAS1 could reverse the positive effects of miR-150-5p mimic and Ad-CCND2 in vitro and in vivo. lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and DbCM development. Thus, ZFAS1 inhibition could be a promising therapeutic target for the treatment and prevention of DbCM.     

Long non-coding RNA OIP5-AS1 promotes pancreatic cancer cell growth through sponging miR-342-3p via AKT/ERK signaling pathway

Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a long non-coding RNA (lncRNA), has been reported to link with the progression of some cancers. However, its biological functions and underlying molecular mechanisms in pancreatic cancer are largely unknown. The aim of this study was to investigate the role of lncRNA OIP5-AS1 in pancreatic cancer. Quantitative real-time PCR analysis revealed that OIP5-AS1 is highly expressed in pancreatic cancer tissues versus adjacent non-tumor tissues. In vitro functional assays showed that downregulation of OIP5-AS1 or overexpression of miR-342-3p inhibited the proliferation, decreased Ki67 expression, and induced cell cycle arrest in pancreatic cancer cells. The expression of cyclinD1, CDK4, and CDK6 was decreased by knockdown of OIP5-AS1. Moreover, we found that OIP5-AS1 acted as a miR-342-3p sponge to suppress its expression and function. Dual-luciferase assay confirmed the interaction of OIP5-AS1 and miR-342-3p and verified anterior gradient 2 (AGR2) as a direct target of miR-342-3p. Results showed that depletion of miR-342-3p abolished the inhibitory effects of OIP5-AS1 knockdown on pancreatic cancer cell growth. The expression of Ki67, AGR2, cyclinD1, CDK4, CDK6, p-AKT, and p-ERK1/2 was reversed by silencing of miR-342-3p in pancreatic cancer cells with OIP5-AS1 knockdown. Further, knockdown of OIP5-AS1 suppressed tumor growth in a xenograft mouse model of pancreatic cancer. OIP5-AS1 induced pancreatic cancer progression via activation of AKT and ERK signaling pathways. Therefore, we demonstrate that OIP5-AS1 functions as oncogene in pancreatic cancer and its downregulation inhibits pancreatic cancer growth by sponging miR-342-3p via targeting AGR2 through inhibiting AKT/ERK signaling pathway.

     

MiR-371-5p Facilitates Pancreatic Cancer Cell Proliferation and Decreases Patient Survival

Background

microRNAs (miRNAs) play a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. To date, scientists have obtained a substantial amount of knowledge with regard to miRNAs in pancreatic cancer. However, the expression and function of miR-371-5p in pancreatic cancer has not been clearly elucidated. The aim of this study was to investigate the roles of miR-371-5p in pancreatic cancer and its association with the survival of patients with pancreatic cancer.

Methods

The expression of miR-371-5p was examined in pancreatic duct adenocarcinoma (PDAC) and their adjacent normal pancreatic tissues (ANPT) or in pancreatic cancer cell lines by qRT-PCR. The association of miR-371-5p expression with overall survival was determined. The proliferation and apoptosis of SW-1990 and Panc-1 cells, transfected with miR-371-5p mimics or inhibitor, were assessed using MTT assay and flow cytometry, respectively. The tumorigenicity was evaluated via mice xenograft experiments. miR-371-5p promoter interactions were analyzed by chromatin immunoprecipitation assays (ChIP). Protein expression was analyzed by Western blot.

Results

The expression level of miR-371-5p was dramatically upregulated in clinical PDAC tissues compared with ANPT. Patients with high miR-371-5p expression had a significantly shorter survival than those with low miR-371-5p expression. The in vitro and in vivo assays showed that overexpression of miR-371-5p resulted in cell proliferation and increased tumor growth, which was associated with inhibitor of growth 1 (ING1) downregulation. Interestingly, we also found that ING1, in turn, inhibited expression of miR-371-5p in the promoter region.

Conclusions

our study demonstrates a novel ING1-miR-371-5p regulatory feedback loop, which may have a critical role in PDAC. Thus miR-371-5p can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.     

miR-497-5p inhibits tumor cell growth and invasion by targeting SOX5 in non–small-cell lung cancer

MicroRNAs plays an important role in the ccurrence and development of non–small-cell lung cancer (NSCLC). miR-497-5p has been reported to function as a tumor suppressor in various cancers. However, the role of miR-497-5p in NSCLC remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of miR-497-5p in NSCLC. Our results showed that the messenger RNA (mRNA) expression level of miR-497-5p was notably downregulated in human NSCLC tissues and cell lines. miR-497-5p overexpression remarkably inhibited NSCLC cell proliferation and increased cell apoptosis in A549 and H460 cells, whereas inhibition of miR-497-5p had an opposite effect. The ability of cell migration and invasion was inhibited by miR-497-5p overexpression but was increased by miR-497-5p inhibition. Moreover, our findings indicated that SOX5 was a direct target of miR-497-5p. The protein and mRNA expression levels of SOX5 in A549 cells were remarkably inhibited by miR-497-5p overexpression but was upregulated by miR-497-5p inhibition. Furthermore, SOX5 overexpression notably reversed the effect of miR-497-5p mimic on NSCLC cell proliferation, cell apoptosis, cell migration, and invasion. Taken together, these results indicated that miR-497-5p overexpression inhibited NSCLC cell proliferation, migration and invasion, and induced cell apoptosis through inhibiting SOX5 gene expression. It was conceivable that miR-497-5p might serve as a potential molecular target for NSCLC treatment.     

Long non-coding RNA ZFAS1 regulates the malignant progression of gastric cancer via the microRNA-200b-3p/Wnt1 axis

Gastric cancer is a common malignant tumor. Studies from our laboratory or others have shown that long non-coding RNA (lncRNA) zinc finger antisense (ZFAS)1 often acts as an oncogene. However, the molecular underpinnings of how ZFAS1 regulates gastric cancer remain to be elucidated. Results showed that ZFAS1 expression was upregulated, and microRNA-200b-3p (miR-200b) expression was downregulated in gastric cancer tissues. MiR-200b overexpression suppressed the proliferation, cell cycle process, and Wnt/β-catenin signaling of gastric cancer cells. Subsequently, we identified miR-200b is a target of ZFAS1 and Wnt1 is a target of miR-200b. Furthermore, promotion of cancer malignant progression and activation of Wnt/β-catenin signaling induced by ZFAS1 was counteracted by increasing miR-200b expression. In vivo, ZFAS1 knockdown suppressed the tumorigenesis with the upregulated miR-200b and the inactive Wnt/β-catenin signaling. Summarily, we demonstrated a critical role of miR-200b in gastric cancer, and ZFAS1 can promote malignant progression through regulating miR-200b mediated Wnt/β-catenin signaling.     

miR-9-5p靶向Ambra1促进舌癌细胞增殖

miRNAs在肿瘤中异常表达,且与肿瘤的发生发展密切相关。目前发现,miR-9-5p在肿瘤中可能发挥原癌或抑癌效应,功能尚未完全阐述清楚。本文拟探讨miR-9-5p在舌癌中的作用。前期研究中收集10例舌癌组织及配对的癌旁组织,实时荧光定量PCR技术检测后发现,miR-9-5p在舌癌组织中的表达量显著高于癌旁组织,且其在舌癌细胞中的表达量也明显高于正常舌上皮细胞。此外,在舌癌细胞Tca8113中过表达miR-9-5p显著增加细胞的增殖能力。生物信息学预测及双荧光素酶报告基因实验证实,miR-9-5p可直接结合在自噬/苄氯素1调节因子1（activating molecule in beclin1-regulated autophagy, Ambra1）的 3′-UTR区域,靶向抑制Ambra1表达。Western印迹结果证实过表达miR-9-5p降低Ambra1的表达,反之亦然。Ambra1在舌癌细胞中的表达量显著低于正常舌上皮细胞。BrdU实验证实在舌癌细胞SCC-25中过表达Ambra1可显著抑制其增殖能力;相反,使用siRNA技术沉默Ambra1能够显著促进Tca8113细胞的增殖。在干预miR-9-5p的细胞中同时干预Ambra1的表达,结果发现Ambra1可显著逆转miR-9-5p对舌癌细胞增殖的促进作用。总之,miR-9-5p在舌癌中可能发挥原癌基因样作用,通过直接靶向抑制Ambra1表达进而促进舌癌细胞发生增殖。     

Long non-coding RNA ZFAS1 sponges miR-484 to promote cell proliferation and invasion in colorectal cancer

The incidence and mortality rate of colorectal cancer (CRC) have been significantly increasing. However, mechanisms involved in CRC progression are still unclear. LncRNA ZFAS1 has been verified as oncogenic molecular in a series of tumors, including CRC. However, the underlying mechanism of ZFAS1 in CRC carcinogenesis remains unclear. In the present study, our data showed that ZFAS1 expression was significantly upregulated in CRC tissues and cell lines. Correlation analysis showed that high ZFAS1 expression was significantly associated with Helicobacter pylori infection, lymph nodes metastasis, advanced TNM stage and poor overall survival of CRC patients. Loss-of-function experiments revealed that ZFAS1 inhibition could markedly suppress CRC cells proliferation and invasion both in vitro and in vivo. Bioinformatics analysis and luciferase reporter assay revealed that ZFAS1 directly interacted with miR-484. Rescue experiments showed that miR-484 inhibitor reversed the tumor suppressing roles of ZFAS1 knockdown on CRC cells. Therefore, our study suggested that ZFAS1 could act as an oncogene in CRC tumorigenesis, and discovered the functional regulatory pathway of ZFAS1 sponging miR-484.     

Retracted: MicroRNA-204-3p represses colon cancer cells proliferation,migration, and invasion by targeting HMGA2

Colon cancer is a detrimental neoplasm of the digestive tract. MicroRNAs (miRNAs) as central regulators have been discovered in colon cancer. Nonetheless, the impact of miR-204-3p on colon cancer remains indistinct. The research attempted to uncover the impacts of miR-204-3p on colon cancer cells growth, migration, and invasion. miR-204-3p expression level in colon cancer tissues and diverse colon cancer cell lines were testified by the quantitative real-time polymerase chain reaction. Exploration of the impacts of miR-204-3p on cell growth, migration, invasion, and their associated factors through assessment of CCK-8, flow cytometry, Transwell, and western blot, respectively. High mobility group AT-hook 2 (HMGA2) expression was then detected in Caco-2 cells after miR-204-3p mimic and inhibitor transfection, additionally dual-luciferase activity was implemented to further uncover the correlation between HMGA2 and miR-204-3p. The impact of HMGA2 on Caco-2 cell growth, migration, and invasion was finally assessed. We found that repression of miR-204-3p was discovered in colon cancer tissues and HCT116, SW480, Caco-2, HT29 and SW620 cell lines. MiR-204-3p overexpression mitigated Coca-2 cell viability, facilitated apoptosis, simultaneously adjusted CyclinD1 and cleaved caspase-3 expression. Cell migration, invasion, and the associated factors were all suppressed by miR-204-3p overexpression. Reduction of HMGA2 was presented in Caco-2 cells with miR-204-3p mimic transfection, and HMGA2 was predicated to be a target gene of miR-204-3p. Besides, HMGA2 silence showed the inhibitory effect on Caco-2 cells growth, migration, and invasion. In conclusion, miR-204-3p repressed colon cancer cell growth, migration, and invasion through targeting HMGA2.     

miR-3940-5p Functions as a Tumor Suppressor in Non–Small Cell Lung Cancer Cells by Targeting Cyclin D1 and Ubiquitin Specific Peptidase-28

miR-3940-5p level was lower in non–small cell lung cancer (NSCLC) tumor tissues than that in the matched tumor-adjacent tissues and correlated with clinicopathological features. Cyclin D1 (CCND1), a key driver of malignant transformation in NSCLC, was overexpressed in many cancers, including NSCLC. The ubiquitin specific peptidase-28 (USP28) was also overexpressed in NSCLC and associated with poor prognosis of NSCLC patients. We searched for miR-3940-5p targets by using TargetScan and miRanda online tools and found that CCND1 and USP28 were potential targets of miR-3940-5p. Based on these findings, we speculated that miR-3940-5p might target CCND1 and USP28 to inhibit NSCLC growth. We determined the expression of miR-3940-5p, CCND1, and USP28 by quantitative real-time polymerase chain reaction and Western blot assays, respectively, and found downregulation of miR-3940-5p and upregulation of CCND1 and USP28 in NSCLC tissues and cell lines. Cell proliferation and apoptosis assays showed that miR-3940-5p suppressed proliferation and promoted apoptosis in NSCLC cells, and silencing CCND1 and USP28 both recapitulated the effects of miR-3940-5p on NSCLC cells. Furthermore, we verified that CCND1 and USP28 were direct targets of miR-3940-5p and also found that the effects of NSCLC cell proliferation and apoptosis by miR-3940-5p were attenuated by overexpression of CCND1 or USP28. The animal experiments also showed that overexpression of miR-3940-5p inhibited the growth of NSCLC tumors in vivo. These results confirmed our speculation that miR-3940-5p inhibits proliferation and induces apoptosis in NSCLC cells by targeting CCND1 and USP28. These findings facilitate a better understanding of the molecular mechanisms underlying NSCLC initiation and progression and provide promising diagnostic markers and therapeutic targets for NSCLC.     

miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells

This study aimed to test the exact functions and potential mechanisms of miR-17-5p in gastric cancer. Using real-time PCR, miR-17-5p was found to be expressed more highly in gastric cancer compared with-normal tissues. Gain- and loss-of-function assays demonstrated that miR-17-5p increased the proliferation and growth of gastric cancer cells in vitro and in vivo. Through reporter gene and western blot assays, SOCS6 was shown to be a direct target of miR-17-5p, and proliferative assays confirmed that SOCS6 exerted opposing function to that of miR-17-5p in gastric cancer. In short, miR-17-5p might function as a pro-proliferative factor by repressing SOCS6 in gastric cancer.     

The putative tumor suppressor microRNA-497 modulates gastric cancer cell proliferation and invasion by repressing eIF4E

Accumulating evidence has shown that microRNAs are involved in multiple processes in gastric cancer (GC) development and progression. Aberrant expression of miR-497 has been frequently reported in cancer studies; however, the role and mechanism of its function in GC remains unknown. Here, we reported that miR-497 was frequently downregulated in GC tissues and associated with aggressive clinicopathological features of GC patients. Further in vitro observations showed that the enforced expression of miR-497 inhibited cell proliferation by blocking the G1/S transition and decreased the invasion of GC cells, implying that miR-497 functions as a tumor suppressor in the progression of GC. In vivo study indicated that restoration of miR-497 inhibited tumor growth and metastasis. Luciferase assays revealed that miR-497 inhibited eIF4E expression by targeting the binding sites in the 3′-untranslated region of eIF4E mRNA. qRT-PCR and Western blot assays verified that miR-497 reduced eIF4E expression at both the mRNA and protein levels. A reverse correlation between miR-497 and eIF4E expression was noted in GC tissues. Taken together, our results identify a crucial tumor suppressive role of miR-497 in the progression of GC and suggest that miR-497 might be an anticancer therapeutic target for GC patients.     

Silencing of circTASP1 inhibits proliferation and induces apoptosis of acute myeloid leukaemia cells through modulating miR-515-5p/HMGA2 axis

Acute myeloid leukaemia (AML) is a common hematopoietic disease that is harmful to the lives of children and adults. CircRNAs are aberrantly expressed in the haematologic malignancy cells. However, the expression of circTASP1 and its function in AML remain unclear. In this study, we showed that circTASP1 was significantly up-regulated in AML peripheral blood samples and cells. Knockdown of circTASP1 inhibited proliferation and promoted apoptosis of HL60 and THP-1 cells in vitro. Bioinformatics prediction and luciferase reporter assay proved that circTASP1 sponged miR-515-5p and negatively regulated miR-515-5p expression in HL60 and THP-1 cells. High mobility group A2 (HMGA2) was proved to be a downstream target of miR-515-5p. The rescue experiments confirmed that knockdown of circTASP1 inhibited proliferation and induced apoptosis by modulating miR-515-5p/HMGA2 pathway. Moreover, the in vivo experiment indicated that knockdown of circTASP1 suppressed tumour growth. In conclusion, circTASP1 acts as a sponge for miR-515-5p to regulate HMGA2, thereby promoting proliferation and inhibiting apoptosis during AML progression. Thus, circTASP1 has the potential to be explored as a therapeutic target for AML treatment.     

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.Subject terms: Gastrointestinal cancer, Non-coding RNAs     

LncRNA-UCA1 modulates progression of colon cancer through regulating the miR-28-5p/HOXB3 axis

Emerging evidence has shown that the long noncoding RNA urothelial carcinoma–associated 1 (UCA1) plays a tumor-promoting role in colorectal cancer, while miR-28-5p shows tumor-inhibitory activity in several tumor types. However, the mechanisms both of these in colon cancer progression are still unknown. In this work, the detailed roles and mechanisms of UCA1 and its target genes in colon cancer were studied. The results showed that UCA1 was upregulated in colon cancer tissues when compared with the adjacent nonhumorous tissues, as well as in the various colon cancer cell lines, but the expression of miR-28-5p showed an opposite trend. Furthermore, a high UCA1 level in colon cancer tissues is positively associated with the tumor size and advanced tumor stages. Functional assays revealed that both UCA1 knockdown and miR-28-5p overexpression could inhibit colon cancer cell growth and migration. Further mechanistic studies indicated that UCA1 knockdown played tumor suppressive roles in SW480 and HT116 cells through binding with miR-28-5p. We also, for the first time, identified HOXB3 as the target gene of miR-28-5p and that HOXB3 overexpression could mediate the functions of UCA1 in cell proliferation and migration of colon cancer cells. In conclusion, our data provided evidence for the regulatory network of UCA1/miR-28-5p/HOXB3 in colon cancer, suggesting that UCA1, miR-28-5p, and HOXB3 are the potential targets for colon cancer therapy.