Linshan Luo

Bio: Linshan Luo is an academic researcher. The author has contributed to research in topics: Gene knockdown & Gene silencing. The author has an hindex of 1, co-authored 3 publications receiving 6 citations.

Circular RNA circCSPP1 knockdown attenuates doxorubicin resistance and suppresses tumor progression of colorectal cancer via miR-944/FZD7 axis.

Abstract: Circular RNAs (circRNAs) have been reported to play vital roles in colorectal cancer (CRC). However, only a few circRNAs have been experimentally validated and functionally described. In this research, we aimed to reveal the functional mechanism of circCSPP1 in CRC. 36 DOX sensitive and 36 resistant CRC cases participated in this study. The expression of circCSPP1, miR-944 and FZD7 were detected by quantitative real time polymerase chain reaction (qRT-PCR) and the protein levels of FZD7, MRP1, P-gp and LRP were detected by western blot. Cell proliferation, migration, invasion, and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, or flow cytometry analysis, respectively. The interaction between miR-944 and circCSPP1 or frizzled-7 (FZD7) was predicted by Starbase 3.0 and verified by the dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay. Xenograft tumor assay was performed to examine the effect of circCSPP1 on tumor growth in vivo. The expression of circCSPP1 and FZD7 was upregulated while miR-944 expression was downregulated in doxorubicin (DOX)-resistant CRC tissues and cells. CircCSPP1 knockdown significantly downregulated enhanced doxorubicin sensitivity, suppressed proliferation, migration, invasion, and induced apoptosis in DOX-resistant CRC cells. Interestingly, we found that circCSPP1 directly downregulated miR-944 expression and miR-944 decreased FZD7 level through targeting to 3′ untranslated region (UTR) of FZD7. Furthermore, circCSPP1 mediated DOX-resistant CRC cell progression and doxorubicin sensitivity by regulating miR-944/FZD7 axis. Besides, circCSPP1 downregulation dramatically repressed CRC tumor growth in vivo. Our data indicated that circCSPP1 knockdown inhibited DOX-resistant CRC cell growth and enhanced doxorubicin sensitivity by miR-944/FZD7 axis, providing a potential target for CRC therapy.

Long noncoding RNA TUG1 regulates the progression of colorectal cancer through miR-542-3p/TRIB2 axis and Wnt/β-catenin pathway.

Abstract: Colorectal cancer (CRC) is one of the third normal malignancy worldwide. Taurine-upregulated gene 1 (TUG1), a member of long noncoding RNAs (lncRNAs), has been reported to be involved in various cancers. However, the mechanism underlying TUG1 in the progression of CRC remains unclear. The expression of TUG1, microRNA-542-3p (miR-542-3p), and tribbles homolog 2 (TRIB2) in CRC tissues and cells (LoVo and HCT116) were detected by quantitative real-time PCR (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), transwell and flow cytometry assays were employed to evaluate the effects of TUG1 in CRC cells. The interaction between miR-542-3p and TUG1 or TRIB2 were verified by dual-luciferase reporter assay. A xenograft tumor model in nude mice was established to investigate the biological role of TUG1 in CRC in vivo. TUG1 was increased in CRC tissues and cells (LoVo and HCT116) in contrast with adjacent normal tissues and normal intestinal mucous cells (CCC-HIE-2). Downregulation of TUG1 or TRIB2 suppressed the proliferation, migration, invasion, and induced apoptosis in CRC cells. And knockdown of TUG1 repressed tumor growth in vivo. Besides, overexpression of TRIB2 reversed the effects of TUG1 depletion on the progression of CRC. Meanwhile, TUG1 interacted with miR-542-3p and TRIB2 was a target of miR-542-3p. Furthermore, miR-542-3p knockdown or TRIB2 overexpression partly reversed the suppression effect of TUG1 depletion on the Wnt/β-catenin pathway. TUG1 served as a tumor promoter, impeded the progression of CRC by miR-542-3p/TRIB2 axis to inactivate of Wnt/β-catenin pathway, which providing a novel target for CRC treatment.

Circular RNA in disease: Basic properties and biomedical relevance

Abstract: Circular RNAs (circRNAs) represent a class of covalently closed RNA molecules with great diversity in molecular features, functions, and regulatory mechanisms. Emerging advances in our understanding of circRNA biogenesis, nuclear export, and stability control have been made very recently. In particular, novel roles of circRNAs in diverse human diseases are increasingly recognized. Various circRNAs have been found to affect many disease‐relevant pathways through a diverse array of mechanisms, including forming R‐loops, sponging miRNAs or proteins, and translating functional proteins, resulting in different pathological phenotypes. This recent progress calls for a revised view of circRNAs in diseases threatening the lives and health of humans. In this review, we focus on the recently described functional relevance of disease‐associated circRNAs as well as the potential of circRNAs in diverse clinical applications.

CircHAS2 promotes the proliferation, migration, and invasion of gastric cancer cells by regulating PPM1E mediated by hsa-miR-944.

Abstract: Gastric cancer (GC) is considered one of the most common gastrointestinal malignancies worldwide. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors. However, the role and potential regulatory mechanisms of circRNAs in GC remain unclear. In this study, we demonstrated that a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis. In vitro experiments demonstrated that circHAS2 knockdown or the addition of hsa-miR-944 mimics inhibited the proliferation, migration, and invasion ability of GC cells and affected the epithelial-mesenchymal transition. In addition, hsa-miR-944 interacted with protein phosphatase, Mg2+/Mn2+-dependent 1E (PPM1E), and was found to be a target gene of circHAS2. The upregulation of PPM1E reversed the effects of circHAS2 knockout on GC cells. The circHAS2/hsa-miR-944/PPM1E axis may be involved in the progression of GC; thus, circHAS2 may be a potential biomarker and therapeutic target for GC.

Non-Coding RNA and Frizzled Receptors in Cancer

Abstract: Frizzled receptors have been long recognized for their role in Wnt/β-catenin signaling, a pathway known for its tumorigenic effects. More recent studies of frizzled receptors include efforts to understand non-coding RNA (ncRNA) regulation of these receptors in cancer. It has become increasingly clear that ncRNA molecules are important for regulating the expression of both oncogenic and tumor-suppressive proteins. The three most commonly described ncRNA molecules are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Here, we review ncRNA molecules that directly or indirectly affect frizzled protein expression and downstream signaling. Exploring these interactions highlights the potential of incorporating ncRNA molecules into cancer prevention and therapy strategies that target frizzled receptors. Previous investigations of frizzled receptors and ncRNA have established strong promise for a role in cancer progression, but additional studies are needed to provide the substantial pre-clinical evidence required to translate findings to clinical applications.

Hsa_circ_0000098 is a novel therapeutic target that promotes hepatocellular carcinoma development and resistance to doxorubicin

Abstract: Circular RNA (circRNA) is crucial to the progression of hepatocellular cancer (HCC). In addition, Mitochondrial calcium uniporter regulatory factor 1 (MCUR1) is commonly overexpressed in HCC to increase cellular ATP levels. Due to the highly aggressive characteristics of HCC, it is essential to identify new diagnostic biomarkers and therapeutic targets that may facilitate the diagnosis of HCC and the development of effective anti-HCC treatments.A series of in vitro and in vivo experiments were undertaken to investigate the biological importance and underlying mechanisms of circ_0000098 in HCC.The expression of circ_0000098 was higher in HCC tissues compared to paired adjacent tissues. According to the receiver-operating characteristic curves, circ_0000098 functioned as a potential diagnostic tumor marker in HCC. Our experiments indicated that circ_0000098 served as a key oncogenic circRNA to increase HCC cell proliferation and invasion in vitro and HCC progression in vivo. Furthermore, mechanistic investigation demonstrated that by sequestering miR-383 from the 3'-UTR of MCUR1, circ_0000098 positively regulated MCUR1 expression in HCC cells and finally promoted HCC progression. On the other hand, inhibiting circ_0000098 in HCC cells could diminish doxorubicin (DOX) resistance by decreasing P-glycoprotein (P-gp, MDR1) expression and intracellular ATP levels. Either downregulation of MCUR1 or overexpression of miR-383 improved DOX sensitivity in HCC cells. Subsequently, a short hairpin RNA targeting circ_0000098 (referred to as sh-1) and doxorubicin (DOX) were encapsulated into platelets (PLTs), referred to as DOX/sh-1@PLT. Activated DOX/sh-1@PLT through HCC cells resulted in the creation of platelet-derived particles that were capable of delivering the DOX/sh-1 combination into HCC cells and promoting intracellular DOX accumulation. Furthermore, our in vivo experiments showed that DOX/sh-1@PLT can effectively reduce P-gp expression, promote DOX accumulation, and reverse DOX resistance.Our results demonstrated that circ_0000098 is an oncogenic circRNA that promotes HCC development through the miR-383/MCUR1 axis and targeting circ_0000098 with DOX/sh-1@PLT may be a promising and practical therapeutic strategy for preventing DOX resistance in HCC.