Long non­coding RNA HOTTIP enhances the fibrosis of lung tissues by regulating the miR­744­5p/PTBP1 signaling axis.

Fibrosis of lung tissue can induce the occurrence and development of numerous types of lung disease. The expression levels of the long non­coding RNA (lncRNA) HOXA distal transcript antisense RNA (HOTTIP) have been reported to be upregulated during the development of fibrosis in liver tissues, which subsequently activated hepatic stellate cells. However, whether the lncRNA HOTTIP participates in the occurrence and development of lung fibrosis remains unknown. The present study aimed to investigate the role of lncRNA HOTTIP in lung fibrosis and its potential mechanism. In the present study, A549 cells were stimulated with TGF­ß1 to induce lung fibrosis in vitro. A549 was transfected with short hairpin RNA­HOTTP, overexpression­polypyrimidine tract binding protein 1 (PTBP1), microRNA (miR)­744­5p mimic or miR­744­5p to regulate gene expression. Cell proliferation and migration were determined using 5'­ethynl­2'­deoxyuridine and wound healing assays, respectively. The expression levels of α­smooth muscle actin, collagen I, collagen III and fibronectin 1 were analyzed using western blotting. starBase was used to identify molecules that may interact with the lncRNA HOTTIP and dual luciferase reporter assays were used to validate the findings. Moreover, an in vivo lung fibrosis model was established by bleomycin induction in mice. Histological injury was observed using hematoxylin and eosin and masson staining. The results of the present study revealed that the proliferation and migration of A549 cells were both suppressed following the knockdown of HOTTIP. The lncRNA HOTTIP was found to target and downregulate the expression levels of miR­744­5p. The overexpression of miR­744­5p inhibited the proliferation and migration of A549 cells. Furthermore, miR­744­5p targeted and downregulated the expression levels of PTBP1. It was subsequently demonstrated that the overexpression of PTBP1 rescued miR­744­5p­induced suppression of the proliferation and migration of A549 cells. The knockdown of lncRNA HOTTIP expression also relieved the fibrosis of the lung tissues of mice. In conclusion, the results of the present study suggested that the lncRNA HOTTIP may promote the fibrosis of lung tissues by downregulating the expression levels of miR­744­5p and upregulating the expression levels of PTBP1.

Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3.

It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the underlying mechanisms. High expression of HOTTIP was detected in mitomycin-resistant CRC cells. Inhibition of HOTTIP reduced the mitomycin resistance. In the co-culture system of mitomycin-resistant cells or their derived exosomes with CRC cells, the HOTTIP was found to be transferred into the parental cells via extracellular vesicles (EVs) secreted from mitomycin-resistant cells and to contribute to the mitomycin resistance. Based on the bioinformatics databases, possible interaction network of HOTTIP, microRNA-214 (miR-214) and Karyopherin subunit alpha 3 (KPNA3) in CRC was predicted, which was further analyzed by dual-luciferase reporter, RNA binding protein immunoprecipitation and RNA pull-down assays. As HOTTIP down-regulated miR-214 to elevate the KPNA3 expression, HOTTIP enhanced the mitomycin resistance through impairing miR-214-dependent inhibition of KPNA3. Finally, HOTTIP was suggested as an independent factor predicting mitomycin response in patients with CRC. Those data together confirmed the promotive effects of EV-carried HOTTIP on the mitomycin resistance, while targeting HOTTIP might be a promising strategy overcoming drug resistance in CRC.

Visible Light-Driven Self-Powered Device Based on a Straddling Nano-Heterojunction and Bio-Application for the Quantitation of Exosomal RNA.

This paper reports the design and fabrication of a self-powered biosensing device based on TiO2 nanosilks (NSs)@MoS2 quantum dots (QDs) and demonstrates a bioapplication for the quantitative detection of exosomal RNA ( Homo sapiens HOXA distal transcript antisense RNA, HOTTIP). This self-powered device features enhanced power output compared to TiO2 NSs alone. This is attributed to the formation of a heterojunction structure with suitable band offset derived from the hybridization between TiO2 NSs and MoS2 QDs, i.e., the straddling (Type I) band alignment. The sensitization effect and excellent visible light absorption provided by MoS2 QDs can prolong interfacial carrier lifetime and improve energy conversion efficiency. This self-powered biosensing device has been successfully applied in quantitative HOTTIP detection through effective hybridization between a capture probe and HOTTIP. The successful capture of HOTTIP leads to a sequential decrease in power output, which is utilized for ultrasensitive quantitative HOTTIP detection, with a linear relationship of power output change versus the logarithm of HOTTIP concentration ranging from 5 fg/mL to 50 000 ng/mL and a detection limit as low as 5 fg/mL. This TiO2 NSs@MoS2 QDs-based nanomaterial has excellent potential for a superior self-powered device characterized by economical and portable self-powered biosensing. Moreover, this self-powered, visible-light-driven device shows promising applications for cancer biomarker quantitative detection.

Expression levels of long non-coding RNA HOXA distal transcript antisense RNA and metabotropic glutamate receptor 1 in pancreatic carcinoma, and their prognostic values.

As a type of malignant tumor developed at the pancreas, the prognosis of pancreatic carcinoma is usually poor, and >90% patients will sucumb to this disease <5 years after diagnosis. Therefore, early detection and treatment of this disease are important for improving the prognosis of patients. Long non-coding RNAs (lncRNAs) have been proven to serve pivotal functions in the development and progression of various tumors. The lncRNA HOXA distal transcript antisense RNA (HOTTIP), which serves an oncogenic role in different types of malignant tumors, has also been reported to be closely correlated with the migration and invasion of pancreatic carcinoma. In addition, the metabotropic glutamate receptor 1 (mGluR1) is also associated with the progression of various types of human cancer; however, its functionality in pancreatic carcinoma is largely unknown. In the present study, the expression levels of HOTTIP and mGluR1 were compared between pancreatic carcinoma and adjacent normal healthy tissues, and the correlation between these expression levels was analyzed. The prognostic value of HOTTIP and mGluR1 in pancreatic carcinoma was also examined. It was observed that the expression levels of HOTTIP and mGluR1 were upregulated in pancreatic carcinoma tissues and pancreatic carcinoma cells, while the expression of HOTTIP was able to positively affect the expression of mGluR1. In addition, high expression levels of HOTTIP were significantly correlated with the tumor size and distant metastasis. These data suggested that HOTTIP and mGluR1 may potentially serve as biomarkers for the prognosis of pancreatic carcinoma.

Long non-coding RNA HOTTIP is able to predict poor prognosis in various neoplasms: A meta-analysis.

HOXA distal transcript antisense RNA (HOTTIP), a critical oncogenic long non-coding RNA, has been reported to be aberrantly regulated in various cancer types. The present meta-analysis aimed to investigate HOTTIP as a potential clinical applicable prognostic biomarker in malignant neoplasms. Literature collections were performed by searching the electronic databases, PubMed and Web of Science (up to July 20, 2016). All the relevant searches were conducted to identify the association of HOTTIP with the overall survival (OS) rate. A total of six articles consisting of 508 patients were included in the present meta-analysis. The results suggested that the overexpression of HOTTIP is closely correlated with poor OS (hazard ratio=2.28; 95% confidence interval=1.71-3.04; P=0.000). In conclusion, the present meta-analysis has demonstrated that an increased expression level of HOTTIP is correlated with poor OS in different types of cancer, suggesting that HOTTIP potentially serves as a reliable prognostic biomarker in different types of cancer.

Regulatory effect of LncRNA HOTTIP in digestive system neoplasms / 国际外科学杂志

As the crucial member of noncoding RNA family,there is increasing evidence that long noncoding RNA has participated in numerous physiological and pathological processes of organisms.HOXA distal transcript antisense RNA is a long noncoding transcript located at the 5'tip of HOXA.According to research reports,the up-regulation of HOTTIP is closely associated with occurrence and progression of multiple digestive system cancers and promotes the carcinogenesis.The regulatory effect of long noncoding RNA HOXA distal transcript antisense in digestive system neoplasms will be summarized in this article.

Regulatory effect of LncRNA HOTTIP in digestive system neoplasms / 国际外科学杂志

As the crucial member of noncoding RNA family,there is increasing evidence that long noncoding RNA has participated in numerous physiological and pathological processes of organisms.HOXA distal transcript antisense RNA is a long noncoding transcript located at the 5'tip of HOXA.According to research reports,the up-regulation of HOTTIP is closely associated with occurrence and progression of multiple digestive system cancers and promotes the carcinogenesis.The regulatory effect of long noncoding RNA HOXA distal transcript antisense in digestive system neoplasms will be summarized in this article.