Introns span only a quarter of the human genome, yet they host around 60% of all known microRNAs. Emerging evidence indicates the adaptive advantage of microRNAs residing within introns is attributed to their complex co-regulation with transcription and alternative splicing of their host genes. Intronic microRNAs are often co-expressed with their host genes, thereby providing functional synergism or antagonism that is exploited or decoupled in cancer. Additionally, intronic microRNA biogenesis and the alternative splicing of host transcript are co-regulated and intertwined. The importance of intronic microRNAs is under-recognized in relation to the pathogenesis of cancer.

Splice and Dice: Intronic microRNAs, Splicing and Cancer.

Nonsmall‐cell lung carcinoma (NSCLC) is one of the deadliest malignancies in the world. LncRNAs are confirmed to be involved in the progression of NSCLC. Meanwhile, lncRNA CRNDE is known to be upregulated in NSCLC; however, the mechanism by which CRNDE regulates the tumourigenesis of NSCLC remains unclear. To test the function of CRNDE in NSCLC, cell proliferation, invasion, and migration were investigated by colony formation and Transwell assays, respectively. qPCR and Western blotting were applied to test gene and protein levels. In addition, the relationship among CRNDE, miR‐455‐3p, and HDAC2 was explored by dual‐luciferase and RIP assays. The data revealed that the expression of CRNDE was upregulated in NSCLC tissues, while miR‐455‐3p was downregulated. CRNDE knockdown inhibited the viability, migration and invasion of NSCLC cells or epidermal growth factor receptor gene (EGFR)‐mutant NSCLC cells. Moreover, inhibition of miR‐455‐3p exhibited the opposite effect. CRNDE bound with miR‐455‐3p, and HDAC2 was found to be targeted by miR‐455‐3p. Meanwhile, miR‐455‐3p downregulation reversed the effect of CRNDE knockdown on NSCLC cell function. Furthermore, miR‐455‐3p notably inhibited the growth and invasion of NSCLC cells via downregulation of HDAC2. Knockdown of CRNDE attenuated NSCLC progression via modulation of the miR‐455‐3p/HDAC2 axis. Thus, those findings might provide a novel strategy against NSCLC.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/kjm2.12558

Silencing of lncRNA CRNDE attenuates nonsmall‐cell lung cancer progression by mediating the miR‐455‐3p/HDAC2 axis

Rab22a promotes the proliferation, migration, and invasion of lung adenocarcinoma via up-regulating PI3K/Akt/mTOR signaling pathway.

MicroRNAs are a group of short non-coding RNAs (miRNAs), which are epigenetically involved in gene expression and other cellular biological processes and can be considered as potential biomarkers for cancer detection and support for treatment management. This review aims to amass the evidence in order to reach the molecular mechanism and clinical significance of miR-877 in different types of cancer. Dysregulation of miR-877 level in various types of malignancies as bladder cancer, cervical cancer, cholangiocarcinoma, colorectal cancer (CRC), gastric cancer, glioblastoma, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma, laryngeal squamous cell carcinoma, melanoma, non-small cell lung cancer (NSCLC), oral squamous cell carcinoma, ovarian cancer (OC), pancreatic ductal adenocarcinoma, and renal cell carcinoma (RCC) have reported, significantly increase or decrease in its level, which can be indicated to its function as oncogene or tumor suppressor. MiR-877 is involved in cell proliferation, migration, and invasion through cell cycle pathways in cancer. MiR-877 could be potential a candidate as a valuable biomarker for prognosis in various cancers. Through this study, we proposed that miR-877 can potentially be a candidate as a prognostic marker for early detection of tumor development, progression, as well as metastasis.

A Comprehensive Study on Signal Transduction and Therapeutic Role of miR-877 in Human Cancers

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death in both men and women. microRNAs (miRs) can exert important functions in cancer development. However, the role of miR-877 in NSCLC as it relates to tartrate resistant acid phosphatase 5 (ACP5) is unknown. For this study, the gain-and-loss-of-function experiments were performed to explore the effects of miR-877 and ACP5 on NSCLC. miR-877 expression in LC and paracancerous tissues, lung epithelial cell line and NSCLC cell lines was detected, and the association between miR-877 expression and clinical features of LC patients was analyzed. The levels of ACP5, epithelial-mesenchymal transition (EMT) markers and apoptosis-related proteins were measured. In vivo experiments were conducted for further validation. Consequently, we found that miR-877 expression was lowered in LC tissues and cell lines, and correlated with clinical stage, differentiation, lymph node metastasis and prognosis of NSCLC patients. Additionally, miR-877 was determined to inhibit ACP5 activity, and miR-877 downregulated the PI3K/AKT pathway by silencing ACP5. Furthermore, overexpression of miR-877 inhibited the viability, migration, invasion and EMT of NSCLC cells, but promoted cell apoptosis. In conclusion, miR-877 overexpression inhibited malignant biological behaviors of NSCLC cells by downregulating ACP5 and inactivating the PI3K/AKT pathway.

microRNA-877 contributes to decreased non-small cell lung cancer cell growth via the PI3K/AKT pathway by targeting tartrate resistant acid phosphatase 5 activity

Wei Zheng

Papers

microRNA-877 contributes to decreased non-small cell lung cancer cell growth via the PI3K/AKT pathway by targeting tartrate resistant acid phosphatase 5 activity