Decoding the tumour-modulatory roles of LIMK2.

LIM domains kinase 2 (LIMK2) is a 72 kDa protein that regulates actin and cytoskeleton reorganization. Once phosphorylated by its upstream activator (ROCK1), LIMK2 can phosphorylate cofilin to inactivate it. This relieves the levering stress on actin and allows polymerization to occur. Actin rearrangement is essential in regulating cell cycle progression, apoptosis, and migration. Dysregulation of the ROCK1/LIMK2/cofilin pathway has been reported to link to the development of various solid cancers such as breast, lung, and prostate cancer and liquid cancer like leukemia. This review aims to assess the findings from multiple reported in vitro, in vivo, and clinical studies on the potential tumour-regulatory role of LIMK2 in different human cancers. The findings of the selected literature unraveled that activated AKT, EGF, and TGF-ß pathways can upregulate the activities of the ROCK1/LIMK2/cofilin pathway. Besides cofilin, LIMK2 can modulate the cellular levels of other proteins, such as TPPP1, to promote microtubule polymerization. The tumour suppressor protein p53 can transactivate LIMK2b, a splice variant of LIMK2, to induce cell cycle arrest and allow DNA repair to occur before the cell enters the next phase of the cell cycle. Additionally, several non-coding RNAs, such as miR-135a and miR-939-5p, could also epigenetically regulate the expression of LIMK2. Since the expression of LIMK2 is dysregulated in several human cancers, measuring the tissue expression of LIMK2 could potentially help diagnose cancer and predict patient prognosis. As LIMK2 could play tumour-promoting and tumour-inhibiting roles in cancer development, more investigation should be conducted to carefully evaluate whether introducing a LIMK2 inhibitor in cancer patients could slow cancer progression without posing clinical harms.

Tumour-regulatory role of long non-coding RNA HOXA-AS3.

Dysregulation of long non-coding RNA (lncRNA) HOXA-AS3 has been shown to contribute to the development of multiple cancer types. Several studies have presented the tumour-modulatory role or prognostic significance of this lncRNA in various kinds of cancer. Overall, HOXA-AS3 can act as a competing endogenous RNA (ceRNA) that inhibits the activity of seven microRNAs (miRNAs), including miR-29a-3p, miR-29 b-3p, miR-29c, miR-218-5p, miR-455-5p, miR-1286, and miR-4319. This relieves the downstream messenger RNA (mRNA) targets of these miRNAs from miRNA-mediated translational repression, allowing them to exert their effect in regulating cellular activities. Examples of the pathways regulated by lncRNA HOXA-AS3 and its associated downstream targets include the WNT/ß-catenin and epithelial-to-mesenchymal transition (EMT) activities. Besides, HOXA-AS3 can interact with other cellular proteins like homeobox HOXA3 and HOXA6, influencing the oncogenic signaling pathways associated with these proteins. Generally, HOXA-AS3 is overexpressed in most of the discussed human cancers, making this lncRNA a potential candidate to diagnose cancer or predict the clinical outcomes of cancer patients. Hence, targeting HOXA-AS3 could be a new therapeutic approach to slowing cancer progression or as a potential biomarker and therapeutic target. A drawback of using lncRNA HOXA-AS3 as a biomarker or therapeutic target is that most of the studies that have reported the tumour-regulatory roles of lncRNA HOXA-AS3 are single observational, in vitro, or in vivo studies. More in-depth mechanistic and large-scale clinical trials must be conducted to confirm the tumour-modulatory roles of lncRNA HOXA-AS3 further. Besides, no lncRNA HOXA-AS3 inhibitor has been tested preclinically and clinically, and designing such an inhibitor is crucial as it may potentially slow cancer progression.

Deciphering the roles of aryl hydrocarbon receptor (AHR) in regulating carcinogenesis.

Aryl hydrocarbon receptor (AHR) is a ligand-dependent receptor that belongs to the superfamily of basic helix-loop-helix (bHLH) transcription factors. The activation of the canonical AHR signaling pathway is known to induce the expression of cytochrome P450 enzymes, facilitating the detoxification metabolism in the human body. Additionally, AHR could interact with various signaling pathways such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1α (HIF-1α), nuclear factor ekappa B (NF-κß), estrogen receptor (ER), and androgen receptor (AR) signaling pathways. Over the past 30 years, several studies have reported that various chemical, physical, or biological agents, such as tobacco, hydrocarbon compounds, industrial and agricultural chemical wastes, drugs, UV, viruses, and other toxins, could affect AHR expression or activity, promoting cancer development. Thus, it is valuable to overview how these factors regulate AHR-mediated carcinogenesis. Current findings have reported that many compounds could act as AHR ligands to drive the expressions of AHR-target genes, such as CYP1A1, CYP1B1, MMPs, and AXL, and other targets that exert a pro-proliferation or anti-apoptotic effect, like XIAP. Furthermore, some other physical and chemical agents, such as UV and 3-methylcholanthrene, could promote AHR signaling activities, increasing the signaling activities of a few oncogenic pathways, such as the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways. Understanding how various factors regulate AHR-mediated carcinogenesis processes helps clinicians and scientists plan personalized therapeutic strategies to improve anti-cancer treatment efficacy. As many studies that have reported the roles of AHR in regulating carcinogenesis are preclinical or observational clinical studies that did not explore the detailed mechanisms of how different chemical, physical, or biological agents promote AHR-mediated carcinogenesis processes, future studies should focus on conducting large-scale and functional studies to unravel the underlying mechanism of how AHR interacts with different factors in regulating carcinogenesis processes.

Delineating the tumour-regulatory roles of EYA4.

Eyes absent homolog 4 (EYA4) is a protein that regulates many vital cellular processes and organogenesis pathways. It possesses phosphatase, hydrolase, and transcriptional activation functions. Mutations in the Eya4 gene can cause sensorineural hearing loss and heart disease. In most non-nervous system cancers such as those of the gastrointestinal tract (GIT), hematological and respiratory systems, EYA4 acts as a putative tumor suppressor. However, in nervous system tumors such as glioma, astrocytoma, and malignant peripheral nerve sheath tumor (MPNST), it plays a putative tumor-promoting role. EYA4 interacts with various signaling proteins of the PI3K/AKT, JNK/cJUN, Wnt/GSK-3ß, and cell cycle pathways to exert its tumor-promoting or tumor-suppressing effect. The tissue expression level and methylation profiles of Eya4 can help predict the prognosis and anti-cancer treatment response among cancer patients. Targeting and altering Eya4 expression and activity could be a potential therapeutic strategy to suppress carcinogenesis. In conclusion, EYA4 may have both putative tumor-promoting and tumor-suppressing roles in different human cancers and has the potential to serve as a prognostic biomarker and therapeutic agent in various cancer types.

Stem Cells for Cancer Therapy: Translating the Uncertainties and Possibilities of Stem Cell Properties into Opportunities for Effective Cancer Therapy.

Cancer recurrence and drug resistance following treatment, as well as metastatic forms of cancer, are trends that are commonly encountered in cancer management. Amidst the growing popularity of personalized medicine and targeted therapy as effective cancer treatment, studies involving the use of stem cells in cancer therapy are gaining ground as promising translational treatment options that are actively pursued by researchers due to their unique tumor-homing activities and anti-cancer properties. Therefore, this review will highlight cancer interactions with commonly studied stem cell types, namely, mesenchymal stroma/stem cells (MSC), induced pluripotent stem cells (iPSC), iPSC-derived MSC (iMSC), and cancer stem cells (CSC). A particular focus will be on the effects of paracrine signaling activities and exosomal miRNA interaction released by MSC and iMSCs within the tumor microenvironment (TME) along with their therapeutic potential as anti-cancer delivery agents. Similarly, the role of exosomal miRNA released by CSCs will be further discussed in the context of its role in cancer recurrence and metastatic spread, which leads to a better understanding of how such exosomal miRNA could be used as potential forms of non-cell-based cancer therapy.

Addressing the Clinical Feasibility of Adopting Circulating miRNA for Breast Cancer Detection, Monitoring and Management with Artificial Intelligence and Machine Learning Platforms.

Detecting breast cancer (BC) at the initial stages of progression has always been regarded as a lifesaving intervention. With modern technology, extensive studies have unraveled the complexity of BC, but the current standard practice of early breast cancer screening and clinical management of cancer progression is still heavily dependent on tissue biopsies, which are invasive and limited in capturing definitive cancer signatures for more comprehensive applications to improve outcomes in BC care and treatments. In recent years, reviews and studies have shown that liquid biopsies in the form of blood, containing free circulating and exosomal microRNAs (miRNAs), have become increasingly evident as a potential minimally invasive alternative to tissue biopsy or as a complement to biomarkers in assessing and classifying BC. As such, in this review, the potential of miRNAs as the key BC signatures in liquid biopsy are addressed, including the role of artificial intelligence (AI) and machine learning platforms (ML), in capitalizing on the big data of miRNA for a more comprehensive assessment of the cancer, leading to practical clinical utility in BC management.

Unveiling the tumour-regulatory roles of miR-1275 in cancer.

The rapid development of small RNA and molecular biology research in the past 20 years has enabled scientists to discover many new miRNAs that are proven to play essential roles in regulating the development of different cancer types. Among these miRNAs, miR-1275 is one of the well-studied miRNAs that has been described to act as a tumour-promoting or tumour-suppressing miRNA in various cancer types. Even though miR-1275 has been widely reported in different original research articles on its roles in modulating the progression of different cancer types, however, there is scarce an in-depth review that could constructively summarize the findings from different studies on the regulatory roles of miR-1275 in different cancer types. To fill up this literature gap, therefore, this review was aimed to provide an overview and summary of the roles of miR-1275 in modulating the development of different cancers and to unravel the mechanism of how miR-1275 regulates cancer progression. Based on the findings summarized from various sources, it was found that miR-1275 plays a vital role in regulating various cellular signaling pathways like the PI3K/AKT, ERK/JNK, MAPK, and Wnt signaling pathways, and the dysregulation of this miRNA has been shown to contribute to the development of multiple cancer types such as cancers of the liver, breast, lung, gastrointestinal tract and genitourinary tract. Therefore, miR-1275 has great potential to be employed as a biomarker to diagnose cancer and to predict the prognosis of cancer patients. In addition, by inhibiting the expression of its unique downstream targets that are involved in regulating the mentioned cellular pathways, this miRNA could also be utilized as a novel therapeutic agent to halt cancer development.

Unraveling the roles of miRNAs in regulating epithelial-to-mesenchymal transition (EMT) in osteosarcoma.

Osteosarcoma is one of the most prevalent primary bone tumors with a high metastatic and recurrence rate with poor prognosis. MiRNAs are short and non-coding RNAs that could regulate various cellular activities and one of them is the epithelial-to-mesenchymal transition (EMT). Osteosarcoma cells that have undergone EMT would lose their cellular polarity and acquire invasive and metastatic characteristics. Our literature search showed that many pre-clinical and clinical studies have reported the roles of miRNAs in modulating the EMT process in osteosarcoma and compared to other cancers like breast cancer, there is a lack of review article which effectively summarizes the various roles of EMT-regulating miRNAs in osteosarcoma. This review, therefore, was aimed to discuss and summarize the EMT-promoting and EMT-suppressing roles of different miRNAs in osteosarcoma. The review would begin with the discussion on the concepts and principles of EMT, followed by the exploration of the diverse roles of EMT-regulating miRNAs in osteosarcoma. Subsequently, the potential use of miRNAs as prognostic biomarkers in osteosarcoma to predict the likelihood of metastases and as therapeutic agents would be discussed.

Current diagnostic approaches to detect two important betacoronaviruses: Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two common betacoronaviruses, which are still causing transmission among the human population worldwide. The major difference between the two coronaviruses is that MERS-CoV is now causing sporadic transmission worldwide, whereas SARS-CoV-2 is causing a pandemic outbreak globally. Currently, different guidelines and reports have highlighted several diagnostic methods and approaches which could be used to screen and confirm MERS-CoV and SARS-CoV-2 infections. These methods include clinical evaluation, laboratory diagnosis (nucleic acid-based test, protein-based test, or viral culture), and radiological diagnosis. With the presence of these different diagnostic approaches, it could cause a dilemma to the clinicians and diagnostic laboratories in selecting the best diagnostic strategies to confirm MERS-CoV and SARS-CoV-2 infections. Therefore, this review aims to provide an up-to-date comparison of the advantages and limitations of different diagnostic approaches in detecting MERS-CoV and SARS-CoV-2 infections. This review could provide insights for clinicians and scientists in detecting MERS-CoV and SARS-CoV-2 infections to help combat the transmission of these coronaviruses.

Transfection types, methods and strategies: a technical review.

Transfection is a modern and powerful method used to insert foreign nucleic acids into eukaryotic cells. The ability to modify host cells' genetic content enables the broad application of this process in studying normal cellular processes, disease molecular mechanism and gene therapeutic effect. In this review, we summarized and compared the findings from various reported literature on the characteristics, strengths, and limitations of various transfection methods, type of transfected nucleic acids, transfection controls and approaches to assess transfection efficiency. With the vast choices of approaches available, we hope that this review will help researchers, especially those new to the field, in their decision making over the transfection protocol or strategy appropriate for their experimental aims.

Single-cell RNA sequencing in human lung cancer: Applications, challenges, and pathway towards personalized therapy.

Lung cancer is one of the most prevalent human cancers, and single-cell RNA sequencing (scRNA-seq) has been widely used to study human lung cancer at the cellular, genetic, and molecular level. Even though there are published reviews, which summarized the applications of scRNA-seq in human cancers like breast cancer, there is lack of a comprehensive review, which could effectively highlight the broad use of scRNA-seq in studying lung cancer. This review, therefore, was aimed to summarize the various applications of scRNA-seq in human lung cancer research based on the findings from different published in vitro, in vivo, and clinical studies. The review would first briefly outline the concept and principle of scRNA-seq, followed by the discussion on the applications of scRNA-seq in studying human lung cancer. Finally, the challenges faced when using scRNA-seq to study human lung cancer would be discussed, and the potential applications and challenges of scRNA-seq to facilitate the development of personalized cancer therapy in the future would be explored.

Regulation of autophagy by microRNAs in human breast cancer.

Breast cancer is the most common solid cancer that affects female population globally. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate post-transcriptional modification of multiple downstream genes. Autophagy is a conserved cellular catabolic activity that aims to provide nutrients and degrade un-usable macromolecules in mammalian cells. A number of in vitro, in vivo and clinical studies have reported that some miRNAs could modulate autophagy activity in human breast cancer cells, and these would influence human breast cancer progression and treatment response. Therefore, this review was aimed to discuss the roles of autophagy-regulating miRNAs in influencing breast cancer development and treatment response. The review would first introduce autophagy types and process, followed by the discussion of the roles of different miRNAs in modulating autophagy in human breast cancer, and to explore how would this miRNA-autophagy regulatory process affect the disease progression or treatment response. Lastly, the potential applications and challenges of utilizing autophagy-regulating miRNAs as breast cancer biomarkers and novel therapeutic agents would be discussed.

Induction of Apoptosis and Regulation of MicroRNA Expression by (2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) Treatment on MCF-7 Breast Cancer Cells.

(2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes.

Dysregulation of miR-638 in the progression of cancers.

MicroRNA (miRNA) is a form of short, single-stranded and non-coding RNA that is important in regulating the post-transcriptional modification of multiple downstream targets. Many miRNAs have been reported to involve in controlling the progression of human diseases, and one of them is miR-638, which play essential roles in regulating the development of human cancer. By targeting the 3'-ends of its targets, miR-638 can regulate cellular processes including proliferation, invasion, metastases, angiogenesis, apoptosis and inflammation. This review was aimed to summarize current findings on the roles of miR-638 in different human cancers based on the results from various in vitro, in vivo and clinical studies. The biogenesis process and tissue expression, followed by the roles of miR-638 in regulating the development of various human cancers by targeting different downstream targets were covered in this review. The potential applications and challenges of employing miR-638 as cancer biomarker and therapeutic agent were also discussed.

Angiogenesis regulation by microRNAs and long non-coding RNAs in human breast cancer.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are capable of regulating gene expression post-transcriptionally. Since the past decade, a number of in vitro, in vivo, and clinical studies reported the roles of these non-coding RNAs (ncRNAs) in regulating angiogenesis, an important cancer hallmark that is associated with metastases and poor prognosis. The specific roles of various miRNAs and lncRNAs in regulating angiogenesis in breast cancer, with particular focus on the downstream targets and signalling pathways regulated by these ncRNAs will be discussed in this review. In light of the recent trend in exploiting ncRNAs as cancer therapeutics, the potential use of miRNAs and lncRNAs as biomarkers and novel therapeutic agent against angiogenesis was also discussed.

Role of miRNAs in regulating responses to radiotherapy in human breast cancer.

Breast cancer is the most common type of cancer that affects females globally. Radiotherapy is a standard treatment option for breast cancer, where one of its most significant limitations is radioresistance development. MicroRNAs (miRNAs) are small, non-protein-coding RNAs that have been widely studied for their roles as disease biomarkers. To date, several in vitro, in vivo, and clinical studies have reported the roles of miRNAs in regulating radiosensitivity and radioresistance in breast cancer cells. This article reviews the roles of miRNAs in regulating treatment response toward radiotherapy and the associating cellular pathways. We identified 36 miRNAs that play a role in mediating radio-responses; 22 were radiosensitizing, 12 were radioresistance-promoting, and two miRNAs were reported to promote both effects. A brief overview of breast cancer therapy options, mechanism of action of radiation, and molecular mechanism of radioresistance was provided in this article. A summary of the latest clinical researches involving miRNAs in breast cancer radiotherapy was also included.

Roles of circulating microRNA(s) in human breast cancer.

miRNAs are short non-coding RNA molecules that regulate the expression of mRNA post-transcriptionally. MiRNAs that are secreted into the circulation, also termed circulating miRNAs, have been studied extensively for their roles in diagnosis, treatment and prognosis of human breast cancer. Breast cancer is the most prevalent female cancer and is associated with key cancer hallmarks including sustained proliferation, evasion of apoptosis, increased invasion, enhanced metastases, initation of inflammation, induction of angiogenesis, metabolic derangement and immune dysregulation. This review aimed to explore the relationships between circulating miRNAs and different breast cancer hallmarks. Besides, the advantages, challenges and clinical application of using circulating miRNAs in human breast cancer management were also discussed.

Evaluation of Khat (Catha edulis) Use as a Risk Factor of Cancer: A Systematic Review.

BACKGROUND: Conducting systematic review to evaluate plant use as a risk factor to cancer could be challenging. A systematic and well-balanced method should be applied to accommodate in vivo and in vitro studies to make a final decision. In this article, khat, a recreational plant used in some Arabic and African regions, was employed as an example to systematically determine its relationships to the premalignant and cancerous conditions. METHODS: Systematic database search was performed to recruit original human, animal or in vitro studies on khat and cancer. Sixteen studies fulfilled the inclusion criteria and subjected to assessment using Risk of Bias (RoB). Office of Health and Translation (OHAT) approach was used to rate the confidence level in the body of evidence. The evidence was integrated to establish the relationships between khat, premalignant conditions and cancer. RESULTS: Seven out of eight studies showed that khat causes premalignant oral lesions with moderate evidence level. Four studies showed that khat causes cancer with low evidence level and another three studies showed that khat has anti-cancer effect with moderate to high evidence level. Only one study suggested that khat is unrelated to cancer. CONCLUSION: RoB and OHAT approach are reliable systematic tools to evaluate plant risk to cancer and provide objective and uniform summary regardless of the study type. In conclusion, our pooled analysis did not find a direct relationship between khat and cancer but anti-cancer effect would require to be proofed on human studies.