Cancer is a global health concern, and the prognosis of patients with cancer is associated with metastasis. Multistep processes are involved in cancer metastasis. Accumulating evidence has shown that cancer cells acquire the capacity of anoikis resistance and anchorage-independent cell growth, which are critical prerequisite features of metastatic cancer cells. Multiple cellular factors and events, such as apoptosis, survival factors, cell cycle, EMT, stemness, autophagy, and integrins influence the anoikis resistance and anchorage-independent cell growth in cancer. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are dysregulated in cancer. They regulate cellular signaling pathways and events, eventually contributing to cancer aggressiveness. This review presents the role of miRNAs and lncRNAs in modulating anoikis resistance and anchorage-independent cell growth. We also discuss the feasibility of ncRNA-based therapy and the natural features of ncRNAs that need to be contemplated for more beneficial therapeutic strategies against cancer.

Pancreatic cancer is malignant and the seventh leading cause of cancer-related deaths worldwide. However, chemotherapy and radiotherapy are—at most—moderately effective, indicating the need for new and different kinds of therapies to manage this disease. It has been proposed that the biologic properties of pancreatic cancer cells are finely tuned by the dynamic microenvironment, which includes extracellular matrix, cancer-associated cells, and diverse immune cells. Accumulating evidence has demonstrated that extracellular vesicles (EVs) play an essential role in communication between heterogeneous subpopulations of cells by transmitting multiplex biomolecules. EV-mediated cell–cell communication ultimately contributes to several aspects of pancreatic cancer, such as growth, angiogenesis, metastasis and therapeutic resistance. In this review, we discuss the role of extracellular vesicles and their cargo molecules in pancreatic cancer. We also present the feasibility of the inhibition of extracellular biosynthesis and their itinerary (release and uptake) for a new attractive therapeutic strategy against pancreatic cancer.

Background/Aim: MicroRNAs (miRNAs) play regulatory roles in pancreatic ductal adenocarcinoma (PDAC). However, it is still required to identify the function of miRNA-301-3p in pancreatic cancer cells. Materials and Methods: Effects of luteolin on cell growth, TRAIL cytotoxicity, and miR-301-3p levels were evaluated. The role of miRNA-301-3p in regulating cell proliferation, target gene expression, and TRAIL cytotoxicity were studied. Results: The levels of miR-301-3p were down-regulated in PANC-1 cells exposed to luteolin, which inhibits the growth of PANC-1 cells and sensitizes cells to TRAIL. The knockdown of miR-301-3p attenuates cell proliferation and enhances TRAIL cytotoxicity. In addition, caspase-8 was directly targeted by miR-301-3p. Conclusion: Our findings unveil a critical biological function of miR-301-3p in regulating cell proliferation and elevating an antiproliferative effect of TRAIL on cancer cells. Our observation of miR-301-3p/caspase-8 relationship can also serve to clarify the role of miR-301-3p in other cancer types and related diseases.Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and a highly fatal malignancy with lymph node or distant metastases upon diagnosis. PDAC is predicted to be the second principal cause of cancer-related deaths by the year 2030 (1). Despite much progress on pancreatic cancer research over the past decades, surgery is the only attempt towards a curative outcome (2). Insufficient clinical efficacy of chemotherapy and radiation therapy has been reported and attributed to drug resistance in PDAC (3-6). Several signaling pathways, including nuclear factor kappa light chain enhancer of activated B cells (NF-ĸB) signaling, are activated, leading to cell growth and metastasis in PDAC. Mutations in tumor suppressor genes are also detected in PDAC (5, 7-9). A better understanding of the molecular characteristics of PDAC can lead to development of novel treatment strategies to combat PDAC.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL has been known to inhibit cell growth by inducing cell-cycle arrest (10,11). In addition, anticancer effects of TRAIL can occur through death receptors 4 and 5, which generally regulate the activation of caspases, a family of cysteine proteases (12-14). Upon TRAIL binding, activation of caspase-8 cleaves executioner caspases, such as caspase-3 and -7, by which effective caspases contribute to chromatin condensation and nuclear fragmentation with the formation of apoptotic bodies (12-15). Indeed, TRAIL-induced apoptosis is impeded by the low expression of death receptors and caspases (16-18). Moreover, TRAIL resistance is associated with FADD-like ICE inhibitory proteins (FLIP) and inhibitor of apoptosis (IAP) family, such as cIAP, XIAP, and survivin, which inhibit the activation of caspases (19). Accumulating evidence has shown that combination of TRAIL with cancer therapeutic agents is effective to subdue TRAIL resistance. For instance, trea...

Cancer is a global health concern and one of the main causes of disease-related death. Even with considerable progress in investigations on cancer therapy, effective anti-cancer agents and regimens have thus far been insufficient. There has been compelling evidence that natural phytochemicals and their derivatives have potent anti-cancer activities. Plant-based anti-cancer agents, such as etoposide, irinotecan, paclitaxel, and vincristine, are currently being applied in medical treatments for patients with cancer. Further, the efficacy of plenty of phytochemicals has been evaluated to discover a promising candidate for cancer therapy. For developing more effective cancer therapy, it is required to apprehend the molecular mechanism deployed by natural compounds. MicroRNAs (miRNAs) have been realized to play a pivotal role in regulating cellular signaling pathways, affecting the efficacy of therapeutic agents in cancer. This review presents a feature of phytochemicals with anti-cancer activity, focusing mainly on the relationship between phytochemicals and miRNAs, with insights into the role of miRNAs as the mediators and the regulators of anti-cancer effects of phytochemicals.

Therapeutic resistance is an inevitable impediment towards effective cancer therapies. Evidence accumulated has shown that the signaling pathways and related factors are fundamentally responsible for therapeutic resistance via regulating diverse cellular events, such as epithelial-to-mesenchymal transition (EMT), stemness, cell survival/apoptosis, autophagy, etcetera. Noncoding RNAs (ncRNAs) have been identified as essential cellular components in gene regulation. The expression of ncRNAs is altered in cancer, and dysregulated ncRNAs participate in gene regulatory networks in pathological contexts. An in-depth understanding of molecular mechanisms underlying the modulation of therapeutic resistance is required to refine therapeutic benefits. This review presents an overview of the recent evidence concerning the role of human ncRNAs in therapeutic resistance, together with the feasibility of ncRNAs as therapeutic targets in pancreatic cancer.